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Columbia  fHmbersittp 
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College  of  <Pfjj>fi!tctan£(  anb  burgeons; 


Reference  Hibrarp 


Digitized  by  the  Internet  Archive 

in  2010  with  funding  from 

Open  Knowledge  Commons 


http://www.archive.org/details/surgeryofpancreaOOswee 


THE  SURGERY  OF  THE  PANCREAS 

BY  J.  E.  SWEET,  A.M.,  M.D. 

Assistant  Professor  of  Surgical  Research,  University  of  Pennsylvania,  Philadel- 
phia. Awarded  the  Alvarenga  Prize  of  the  College  of  Physicians  of  Phila- 
delphia for  1915. 

"  With  each  advance  in  technic  we  reach  a  higher  level  from  which  a  wider 
field  of  vision  is  open  to  us,  and  from  which  we  see  events  previously  out 
of  range." — Pawlow. 

1.  Introduction.  12.  Pancreas vergiftung. 

2.  Anatomy  of  the  Pancreas.  13.  The   Relation    of   the   Pancreas    to 

3.  The  Blood-vessels.  High  Intestinal  Obstruction. 

4.  The  Lymphatics.  14.  The  Pathology. 

5.  The  Nerves.  15.  Chronic  and  Acute  Pancreatitis. 

6.  The  Microscopic  Anatomy.  16.  The  Factor  of  Safety  in  Physiology 

7.  The  Surgical  Anatomy.  and  Surgery. 

8.  The  Embryology.  17.  The   Diagnosis   of   Pancreatic   Dis- 

9.  The  Physiology.  ease. 

10.  Internal  Secretion.  18.  Pancreatoenterostomy. 

11.  The  Relation  to  the  Ductless  Glands.      19.  The  Surgery. 

20.  Conclusions. 

INTRODUCTION 

There  comes  a  time  in  the  affairs  of  men  when  it  is  well  to  pause 
for  a  moment  and  take  an  inventory  of  whatever  is  on  hand,  in  order 
that  one  may  know  what  he  has  as  the  result  of  his  labor  and  what  he 
needs  to  make  his  labor  more  productive. 

I  propose  in  the  following  to  take  stock  of  our  knowledge  concern* 
ing  the  pancreas,  particularly  to  assemble  certain  parts  of  our  knowl- 
edge which  lie  on  the  experimental  shelves,  to  dust  off  the  old  articles 
and  add  certain  new  ones ;  to  see,  when  we  have  our  inventory  com- 
plete, if  we  do  not  have  greater  surgical  assets  than  we  think. 

Of  all  the  organs  of  the  body,  the  pancreas  seems  still  the  one 
most  feared  by  surgeons;  there  are  certain  good  reasons  for  this 
respect,  and  equally  good  reasons  why  this  proper  respect  should  not 
be  allowed  to  grow  to  the  proportions  of  a  noli  me  tangere. 

1 


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INTERNATIONAL    CLINICS 


THE   ANATOMY 


The  pancreas  (nav  tcpta?,  all  flesh,  though  not  necessarily  mean- 
ing muscle  tissue)  retains  the  meaningless  name  given  it  by  the 
ancient  anatomists  in  most  modern  languages  except  the  German, 
which  often  employs  the  term  Bauchspeicheldruse;  but  even  this  im- 
provement does  not  do  justice  to  the  organ,  which  is  far  more  than  a 
salivary  gland.  The  trend  of  modern  investigation  points  strongly 
to  the  suspicion  that  the  pancreas  is  the  most  important  organ  of 
the  body,  not  because  of  its  function  in  the  digestion  of  food,  which 
can  be  entirely  dispensed  with,  but  from  the  point  of  view  of  the 
control  exercised  by  the  pancreas  over  the  functions  of  many  of  the 
other  glands  which  possess  an  internal  secretion,  and  from  the  point 
of  view  of  the  control  by  the  pancreas  of  glucose  metabolism.  The 
importance  of  this  latter  function  is  seen  not  only  in  the  history  of 
our  knowledge  of  diabetes,  but  even  more,  perhaps,  in  the  recently- 
offered  proof  that  a  portion  of  every  protein  molecule  is  available 
for  conversion  into  glucose.  Once  converted  into  glucose,  this  protein 
fraction  becomes  subject  to  the  control  of  the  internal  functions  of 
the  pancreas ;  therefore  the  pancreas  must  be  considered  as  controlling, 
by  its  internal  function,  not  only  carbohydrate  metabolism  as  it  is 
ordinarily  thought  of,  but  also  a  part  of  j3rotein  metabolism. 

The  pancreas  lies  not  only  functionally,  but  anatomically,  at  the 
centre  of  the  abdominal  cavity,  lying  transversely  across  the  spinal 
column  at  the  level  of  the  first  or  second  lumbar  vertebra,  though 
occasionally  higher,  across  the  twelfth  thoracic. 

In  shape  Meckel  compared  the  pancreas  to  a  sort  of  hammer; 
Verneuil  to  a  cross  placed  on  its  side,  the  short  vertical  arm  repre- 
senting the  head;  Winslow  compared  it  to  a  dog's  tongue;  Piersol l 
compares  it  with  a  revolver,  the  head  of  the  pancreas  representing 
the  handle  of  the  revolver.  These  descriptions  convey  fully  as 
accurate  a  concept  of  the  form  of  the  organ  as  does  the  division  into 
many  parts  and  surfaces  of  which  the  anatomists  seem  so  fond.  Since 
the  surgeon  has  no  occasion  to  investigate  the  normal  organ,  and 
since  the  normal  picture  is  so  complicated  by  adhesions  and  inflamma- 
tions when  he  does  see  it,  the  relation  of  the  organ  to  surrounding- 
structures  is  of  more  concern  to  him  than  the  normal  form. 

The  head  of  the  pancreas  lies  in  the  curve  of  the  duodenum, 
conforming  to  the  variations  in  position  and  consequent  form  of  the 
duodenum.     On  the  front  of  this  portion  of  the  gland  is  a  groove  for 


SURGERY    OF    THE    PANCREAS  o 

the  gastroduodenal  branch  of  the  hepatic  artery,  this  groove  marking 
anteriorly  the  division  between  head  and  neck.  The  ductus  chole- 
dochus  passes  beneath  the  upper  part  of  the  head  and  the  duodenum, 
and  is  not  uncommonly  entirely  buried  in  the  glandular  tissue  of  the 
pancreas.  Conforming  to  the  variations  in  shape  and  position  of  the 
duodenum,  the  head  of  the  pancreas  may  be  in  close  proximity  on 
the  posterior  surface  to  the  vena  cava,  the  right  renal  vein,  or  the 
right  suprarenal  body.  The  posterior  surface  of  the  portion  called 
the  neck  is  marked  by  a  deep  groove  for  the  portal  vein,  which  vein 
may  be  entirely  surrounded  by  gland  tissue. 

The  posterior  surface  of  the  body  and  tail  of  the  pancreas,  from 
the  deep  portal  groove  to  the  end  of  the  tail,  or  the  splenic  end,  lies 
on  the  vena  cava,  then  on  the  aorta  between  the  cceliac  axis  and  the 
superior  mesenteric  artery,  which  groove  the  pancreas  above  and 
below ;  beyond  this  point  it  lies  on  the  left  pillar  of  the  diaphragm, 
the  left  suprarenal  body,  and  the  left  kidney.  The  end  of  the  tail 
usually  rests  against  the  spleen,  or  may  extend  still  farther  toward 
the  left.  There  are  two  horizontal  grooves  on  the  posterior  pancreas 
surface,  the  smaller  one  above  for  the  splenic  artery  from  near  the 
aorta  to  the  tail,  the  larger  groove  below,  from  the  deep  portal  groove 
to  the  tail,  for  the  splenic  vein.  The  actual  point  where  the  pancreas 
crosses  the  spinal  column  is  represented  by  a  tuberosity  called  the 
tuber  omentale.  The  actual  length  of  the  pancreas  is  variously  given 
by  different  anatomists,  varying  from  Henle's  16  to  22  cm.  to 
Schirmer's  measurements  of  22  to  26  cm.  and  occasionally  30  cm. 

The  relation  between  the  stomach  and  the  pancreas  is  so  intimate 
that  the  ancients  supposed  that  the  pancreas  formed  a  pillow  for  the 
stomach  to  rest  upon.  The  lower  end  of  the  vertical  portion  of  the 
pyloric  end  of  the  stomach  rests  directly  upon  the  tuber  omentale. 
These  relations  with  the  stomach  depend,  however,  upon  the  degree 
of  gastroptosis  present ;  depending  upon  the  position  of  the  stomach, 
cysts  and  tumors  of  the  pancreas  may  present  above,  behind,  or  below 
the  stomach,  and,  if  below,  either  between  the  stomach  and  transverse 
colon  or  below  both  stomach  and  transverse  colon.  These  relations 
are  shown  in  the  diagram,  Fig.  1.*  In  some  patients  with  pronounced 
gastroptosis  the  normal  pancreas  may  be  palpated  above  the  stomach. 

The  relations  of  the  pancreas  to  the  peritoneum  are  such  that  the 

*  My  thanks  are  due  to  Mr.  Erwin  F.  Faber  for  the  accompanying  drawings. 


4  INTERNATIONAL    CLINICS 

pancreas — at  any  rate,  the  body  and  tail — doubtless  shares  less  in  a 
general  visceroptosis  than  any  of  the  other  abdominal  organs.  When 
first  formed  in  the  embryo,  the  pancreas  runs  upward  toward  the 
head,  behind  the  stomach,  and  between  the  layers  of  the  mesogastrium, 
so  that  it  possesses  a  complete  peritoneal  covering.  Subsequently,  as 
a  result  of  the  changes  which  take  place  in  the  position  of  the  stomach, 
the  pancreas  turns  over  on  its  right  side,  and  becomes  adherent  to 
the  posterior  abdominal  wall.  The  peritoneum  of  the  posterior  sur- 
face is  soon  lost  by  absorption,  but  it  persists  on  the  anterior  surface ; 
the  organ,  arising  entirely  intraperitoneal,  has  therefore  become  extra- 
peritoneal. This  retroperitoneal  location,  together  with  the  relation 
to  the  great  vessels,  renders  the  organ  less  movable  than  any  other 
viscus.  The  peritoneal  covering  of  the  anterior  surface  of  the  pancreas 
is  derived  from  the  prolongation  of  the  two  layers  of  the  transverse 
mesocolon,  which  latter  is  attached  to  the  anterior  border  of  the  gland, 
from  the  tail  to  the  neck.  At  this  border  the  two  layers  separate, 
the  anterior,  derived  from  the  lesser  peritoneal  sac,  passing  back- 
wards and  upwards  over  the  superior  pancreatic  surface;  the  pos- 
terior, derived  from  the  greater  peritoneal  sac,  turning  downwards 
and  backwards  along  the  inferior  surface.  The  pancreas  in  cross- 
section  is  roughly  triangular,  with  the  base  against  the  posterior  body 
wall,  the  apex  of  the  triangle,  to  which  the  mesocolon  is  attached, 
towards  the  front,  one  limb  of  the  triangle  forming  the  superior 
pancreatic  surface,  the  other  limb  the  inferior  surface  (Fig.  1). 

As  the  transverse  mesocolon  is  followed  to  the  right  it  ceases,  as  a 
rule ;  that  is,  its  two  layers  fail  to  meet  about  the  neck  of  the  pancreas. 
Beyond  this  the  posterior  surface  of  the  colon  is  generally  free  from 
peritoneum,  and  is  connected  by  areolar  tissue  to  the  front  of  the  head 
of  the  pancreas.  When  the  head  extends  below  the  level  of  the  colon, 
the  pancreas  is  covered  by  the  continuation  downwards  of  the  peri- 
toneum from  the  under  surface  of  the  colon.  Often  the  transverse 
mesocolon  is  continued  to  the  right  as  far  as  the  hepatic  flexure,  when 
the  anterior  surface  of  the  head  is  completely  covered  by  peritoneum. 

THE  BLOOD-VESSELS 

The  arteries  of  the  pancreas  are:  (1)  The  superior  pancreatico- 
duodenal, a  branch  of  the  gastroduodenal  artery,  which  runs  down  on 
the  front  of  the  head,  sending  branches  outwards  to  the  duodenum, 


Fig.  1. 


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T.W. 


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The  relation  of  the  pancreas  to  the  greater  and  lesser  peritoneal  cavities,  and  to  the  stomach, 
colon,  duodenum,  and  the  retroperitoneal  space.  (Modified  from  the  diagram  of  Piersol.)  G.  H.  L., 
gastrohepatic  ligament;  M.,  mesocolon;  G.  E.  L.,  gastro-epiploic  ligament;  F.  W.,  foramen  of  Win- 
slow,  with  arrow  passing  through  the  foramen  from  the  greater  to  the  lesser  peritoneal  sac;  P., 
pancreas;  £>.,  duodenum;  G.  P.  C,  greater  peritoneal  cavity. 


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SUEGERY    OF    THE    PANCKEAS  5 

as  well  as  numerous  twigs  into  the  substance  of  the  pancreas.  (2) 
The  inferior  pancreaticoduodenal,  a  branch  of  the  upper  part  of  the 
superior  mesenteric  artery;  it  runs  upwards  and  to  the  right  across 
the  back  of  the  head,  and  sends  branches  to  it  and  to  the  duodenum, 
one  of  which  runs  between  the  head  and  the  duodenum.  These  two 
pancreaticoduodenal  arteries  anastomose  around  the  inferior  border 
of  the  head.  (3)  The  inferior  pancreatic  branch  of  the  superior 
mesenteric  (or  sometimes  of  the  gastroduodenal)  artery,  a  consider- 
able branch,  which  arises  along  with  or  near  the  last,  and  runs  to  the 
left  along  the  lower  border  of  the  pancreas,  often  even  as  far  as  the 
tail.  (4)  Pancreatic  branches  of  the  splenic  artery  are  several  (three 
to  five)  fair-sized  branches  which  come  off  from  the  splenic  as  it  runs 
behind  the  upper  border  of  the  gland ;  they  enter  the  pancreas  imme- 
diately, and  traverse  its  substance  from  above  downwards,  some  send- 
ing branches  in  both  directions  along  the  course  of  the  pancreatic 
duct.  (5)  Small  pancreatic  branches  also  arise  from  the  hepatic 
artery  while  it  rests  on  the  upper  part  of  the  gland  and  enter  it 
immediately.  One  of  the  latest  descriptions  of  the  arteries  of  the 
pancreas  varies  slightly  from  the  one  I  have  given  (Do  Kio  Branco)  ;  2 
but  it  is  not  unlikely  that  slight  variations,  perhaps  appearing  as 
racial  constants,  might  occur  in  the  arterial  distribution  of  an  organ 
so  richly  supplied  (Fig.  2). 

The  veins  of  the  pancreas  are:  (1)  An  anterior  pancreatico- 
duodenal, which  passes  downwards  and  to  the  left  on  the  front  of  the 
head  and  joins  the  superior  mesenteric;  (2)  a  posterior  pancreatico- 
duodenal, which  crosses  the  back  of  the  head  and  opens  into  the  portal 
vein;  (3)  several  small  pancreatic  veins  which  join  the  splenic;  and 
(4)  some  from  the  upper  part  of  the  head  and  neck  join  the  portal, 
which  latter  vein  ultimately  receives  all  the  blood  returned  from  the 
gland. 

THE   LYMPHATICS 

The  only  complete  summary  of  the  lymphatics  of  the  pancreas 
and  their  relations  with  the  general  lymph  system  of  the  abdomen  is 
to  be  found  in  the  work  of  Bartels.3  There  exists  throughout  the 
pancreas  a  perilobular  network  of  lymph-vessels;  these  vessels  an- 
astomose with  a  similar  network  of  lymphatics  in  the  wall  of  the 
duodenum  and  with  the  lymphatics  of  other  adjoining  structures. 
In  his  first  paper  Bartels  seemed  to  think  that  these  lymph-channels 


6  INTERNATIONAL    CLINICS 

from  the  duodenum  extend  directly  into  the  pancreas ;  in  his  second 
contribution  he  corrects  this  idea,  having  convinced  himself  that  these 
lymph-channels  from  the  gut  do  not  run  directly  into  the  pancreatic 
lymphatics,  but  join  these  latter  lymph-channels,  and  the  two  con- 
tinue in  a  common  vessel  to  the  nearest  regional  lymph-gland.  Bartels 
appreciates  the  clinical  significance  of  his  findings,  and  cites  cases 
from  Oser's  4  work  to  substantiate  his  suspicion  that  certain  cases  of 
pancreatic  disease  may  be  due  to  the  entrance  of  microorganisms  by 
way  of  the  lymphatics.  The  afferent  lymph-vessels  of  the  pancreas 
are  divided  into  four  groups- — a  left,  superior,  right,  and  inferior 
group.  The  vessels  follow  the  general  law  of  lymphatic  distribution, 
that  every  organ  sends  its  lymphatics  to  the  nearest  regional  glands, 
following  in  this  scheme  the  general  distribution  of  the  blood-vessels. 
The  multiple  blood  supply  of  the  pancreas  therefore  explains  the 
numerous  lymphatic  connections.  Toward  the  left,  lymph-vessels  run 
from  the  tail  of  the  pancreas  to  the  pancreaticosplenic  lymph-nodes 
and  to  the  hilus  of  the  spleen. 

Superiorly  the  channels  run  to  the  superior  pancreatic  nodes, 
especially  to  those  in  the  neighborhood  of  the  cardia,  and  to  the 
hepatic  nodes.  Toward  the  right  the  afferent  vessels  pass  to  the 
anterior  and  posterior  pancreaticoduodenal  nodes.  Inferiorly  the 
vessels  pass  to  the  periaortic,  the  mesenteric,  the  mesocolic,  and  the 
inferior  pancreatic  nodes.  In  addition  to  these  afferent  vessels  pass- 
ing to  the  regional  glands,  anastomoses  exist  with  the  lymphatics  of 
the  duodenum,  the  mesocolon,  the  mesentery,  the  ductus  choledochus, 
the  gall-bladder,  and  the  hilus  of  the  liver,  and  possibly  with  the  left 
suprarenal  (Fig.  3).  The  possibilities  for  the  metastatic  spread  of 
carcinoma  of  the  pancreas  would  seem  excellent;  the  surgical  pos- 
sibilities of  a  complete  removal  of  carcinoma  of  the  pancreas  and 
adjacent  lymph-nodes  seem  hardly  excellent.  The  possibilities  of 
pancreatic  involvement  in  diseases  of  neighboring  organs  have,  as  we 
shall  see,  been  granted  their  full  surgical  significance  by  Deaver. 

Franke  5  has  made  a  special  study  of  the  lymphatics  of  the  gall- 
bladder and  bile  ducts  and  their  relation  to  the  head  of  the  pancreas 
(Fig.  4).  He  has  shown  in  this  work  that  the  lymphatics  of  the 
upper  part  of  the  head  of  the  pancreas  can  be  injected  from  the  gall- 
bladder. 


Fig.  3. 


The  relation  of  the  lymphatics  of  the  human  pancreas  to  the  regional  lymph-nodes.    (From  Bartels.) 
S.,  stomach  turned  toward  the  right;  C,  cardia;  L.,  stump  of  liver;  Sp.,  spleen. 


SURGERY  OF  THE  PANCREAS 


THE  NERVES 


The  nerves  of  the  pancreas  are  derivates  of  the  sympathetic 
system,  through  the  cceliac  ganglion  (plexus  Solaris).  The  nerves 
enter  the  gland  mainly  with  the  arteries,  though  some  enter  inde- 
pendently of  the  arteries  directly  from  the  plexus.  Within  the  gland 
the  nerves  follow  the  arteries,  forming  a  network  about  them,  finally 
surrounding  the  gland  acini  with  a  network  of  nerve-fibres.  Pensa  6 
holds  that  the  nerves  form  a  characteristic  network  between  the  cell 
columns  of  the  islands  of  Langerhans,  and  that  this  nerve  structure, 
differing  from  that  of  the  gland  acini,  points  to  the  conclusion  that 
these  islands  are  not  rudimentary  gland-cells,  but  distinct  structures. 
Sobotta  7  points  out  that  the  occurrence  of  a  few  medullated  fibres  in 
the  pancreas  does  not  necessarily  prove  that  the  cerebrospinal  nerves 
and  the  vagus  take  part  in  the  innervation  of  the  pancreas,  since  the 
splanchnics  contain  medullated  fibres. 

MICROSCOPIC  ANATOMY 

The  finer  anatomy  of  the  pancreas  contains  little  of  especial  sur- 
gical interest.  It  is  an  acino-tubular  gland  similar  in  structure  to 
the  salivary  glands,  and,  like  the  parotid,  subject  to  the  specific  in- 
fection with  mumps.  The  pancreas  contains  certain  cell  structures 
peculiar  to  the  organ,  the  islands  of  Langerhans,  which  have  been 
considered  the  source  of  the  specific  internal  function  of  the  gland 
which  is  concerned  in  the  metabolism  of  glucose,  and  the  loss  of 
which  marks  diabetes  mellitus.  This  matter  cannot  be  considered 
settled ;  the  anatomists  are  about  equally  divided  as  to  the  specific 
nature  of  these  cell  bodies,  one  group  holding  that  the  islands  are 
definite  specific  structures,  the  other  that  they  are  rudimentary  or 
resting  gland-cells ;  likewise  the  physiologists  have  been  unable  to 
offer  definite  proof.  The  literature  on  this  subject  is  very  extensive 
and  ever  growing.8,  9>  10 

SURGICAL  ANATOMY 

The  surgical  anatomy  of  the  pancreas  becomes,  therefore,  ex- 
tremely complicated  because  of  the  intimate  relation  of  the  organ  with 
so  many  important  organs  and  so  many  vital  structures.  The  head 
is  in  definite  relation  to  the  common  duct  and  the  duodenum,  and  to 
the  common  blood  supply  of  head  and  duodenum ;  this  blood  supply  is, 


8  INTERNATIONAL    CLINICS 

in  the  dog,  of  such  importance  that  the  destruction  of  the  common 
artery  may  result  in  necrosis  of  the  duodenum.  The  head  may  be  in 
relation  to  the  right  kidney,  the  right  suprarenal  body,  or  the  vena 
cava.  The  neck  of  the  pancreas  is  in  immediate  contact  with  the 
gastroduodenal  branch  of  the  hepatic  artery  anteriorly,  and  pos- 
teriorly with  the  portal  vein,  which  it  may  surround.  The  body  is 
intimately  associated  with  the  cceliac  axis,  the  aorta,  and  the  superior 
mesenteric  artery,  and  with  the  vena  cava;  the  body  and  tail  with 
the  artery  and  vein  of  the  spleen;  the  tail  with  the  spleen,  the  left 
kidney,  and  the  left  suprarenal  body.  The  pancreas  is  more  or  less 
intimately  associated  with  the  stomach  and  with  the  lesser  peritoneal 
cavity;  it  is  also  in  relation,  below  the  attachment  of  the  mesocolon 
along  the  apex  of  the  gland,  with  the  greater  peritoneal  cavity  (Figs. 
5  and  1).  The  retroperitoneal  location  may  result  in  involvement 
of  the  tissue  surrounding  the  great  vessels.  These  anatomical  rela- 
tions show  why  disease  of  the  pancreas  may  involve  the  common 
duct,  the  duodenum,  or  the  pylorus,  the  cardiac  end  of  the  stomach, 
or  even  compress  the  whole  stomach  against  the  anterior  abdominal 
wall ;  the  colon  or  the  ureter  may  be  involved ;  or  the  portal  vein,  the 
vena  cava,  aorta,  splenic  vessels,  or  the  superior  mesenteric  vein; 
further,  these  relations  show  how  disease  of  these  adjacent  structures 
may,  conversely,  involve  the  pancreas.  A  tumor  of  the  pancreas 
extending  toward  the  right  may  produce  jaundice  and  intestinal 
obstruction;  extending  upwards,  the  same  symptoms,  plus  pyloric 
obstruction  and  gastric  dilatation ;  extending  backwards,  by  pressure 
on  the  retroperitoneal  lymphatics,  ascites  and  oedema  of  the  lower 
limbs. 

It  is  apparent,  from  these  relations,  and  from  a  glance  at  Fig.  1, 
that  the  pancreas  may  be  approached  surgically  either  from  the  front 
or  the  back ;  the  approach  through  an  anterior  incision  would  proceed 
either  above  the  stomach,  through  the  gastrohepatic  omentum,  below 
the  stomach,  through  the  gastro-epiploic  omentum,  or  below  both 
stomach  and  colon,  through  the  mesocolon.  The  choice  of  route 
would  depend  upon  the  position  of  the  stomach  in  the  individual 
patient.  From  the  back  the  body  is  approachable  at  the  costovertebral 
junction,  the  tail  through  an  incision  extending  from  the  tip  of  the 
twelfth  rib  anteriorly. 

A  result  of  the  anatomical  position  of  the  pancreas  is  the  very 


Fig.  4. 


The  relation  of  the  lymphatics  of  the  gall-bladder  to  the  head  of  the  pancreas.     (From  Frankc.) 


SURGERY    OF    THE    PANCREAS  9 

complete  protection  afforded  by  this  location  from  the  effects  of 
external  violence.  This  protection  is,  however,  not  perfect,  as  shown 
by  the  cases  of  complete  subcutaneous  transverse  rupture  of  the 
pancreas  which  have  been  reported.11' 12,  13,  14 

THE    EMBRYOLOGY 

The  pancreas  arises  from  one  dorsal  and  one  or  two  ventral 
Anlagen,  budding  out  of  the  primitive  gut,  the  dorsal  Anlage  nearer 
the  stomach,  the  ventral  Anlage  or  Anlagen  in  close  relationship  with 
the  ductus  choledochus.  These  primary  diverticula  give  off  hollow 
buds,  which  in  their  turn  give  off  others,  and  this  process  is  continued 
until  the  mass  of  the  gland  is  formed  (Fig.  6).  The  terminal 
buds  thus  produced  develop  into  the  gland  acini,  while  the  others 
form  the  gland  ducts.  The  latest  authorities  speak  of  three  Anlagen, 
one  dorsal  and  two  ventral,  of  which  the  left  ventral  soon  retrogresses, 
or  never  develops  beyond  a  rudimentary  stage.  As  the  digestive  tube 
now  grows  in  length,  together  with  the  lengthening  of  the  ductus 
choledochus,  the  persisting  ventral  portion  becomes  further  removed 
from  the  duodenum,  its  ducts  fuse  with  the  duct  system  of  the  larger 
dorsal  Anlage,15  and  then,  curiously,  the  duct  system  of  the  smaller 
portion  develops  into  the  most  important  duct,  the  duct  of  Wirsung, 
while  the  glandular  tissue  developing  from  this  Anlage  forms  only  a 
part  of  the  head  and  the  uncinate  process;  the  greater  part  of  the 
pancreas  develops  from  the  dorsal  Anlage,  while  the  duct  system  of 
the  original  Anlage  of  this  portion  becomes  the  slightly-developed 
duct  of  Santorini.  While  this  is  the  general  rule,  variations  may 
occur,  as  seems  natural  from  such  an  involved  mode  of  duct  growth. 
In  a  study  of  one  hundred  subjects  Opie  16  found  two  ducts  in  every 
instance,  but  occasionally  one  or  the  other  was  so  small  that  it  was 
found  with  difficulty.  In  ten  out  of  the  hundred  cases  the  two  ducts 
failed  to  anastomose  within  the  gland,  and  in  four  additional  cases  the 
two  duct  systems  were  united  by  such  a  minute  twig  that  they  might 
be  regarded  as  independent  of  one  another. 

In  twenty  instances  the  duodenal  end  of  the  duct  of  Santorini 
was  not  patent,  and  in  a  considerable  number  of  specimens  the  orifice 
of  the  duct  of  Santorini,  though  patent,  was  so  minute  that  its  func- 
tional significance  was  slight.  In  eleven  out  of  one  hundred  speci- 
mens the  duct  of  Santorini,  on  the  contrary,  was  equal  in  size  to,  or 


10  INTERNATIONAL    CLINICS 

larger  than,  the  duct  of  Wirsung,  so  that  during  life  it  was  doubtless 
the  outlet  for  a  considerable,  if  not  the  larger,  part  of  the  pancreatic 
juice. 

This  matter  of  the  ducts  of  the  pancreas  becomes  of  importance 
in  the  study  of  the  relation  of  pancreatitis  to  gall-bladder  disease, 
and  particularly  to  the  technical  question  of  the  possibility  of  drain- 
ing the  pancreas  through  the  gall-bladder.  Not  only  does  the  develop- 
ment of  the  ducts  result  in  variations  in  the  relative  size  and  func- 
tional importance  of  the  two  ducts,  but  variations  in  the  form  of 
the  actual  union  between  the  duct  of  Wirsung  and  the  ductus  chole- 
dochus  occur,17  as  is  shown  in  Fig.  1.  In  Fig.  1  the  type  of 
communication  is  such  that  a  small  gall-stone  could  block  the  papilla 
of  Vater,  and  drainage  of  the  gall-bladder  would  drain  the  pancreas; 
in  the  type  of  Fig.  3  this  same  condition  might  possibly  occur;  in 
types  2  and  4,  however,  the  pancreas  could  not  be  drained  through 
the  gall-bladder  under  any  conditions.  This  matter  of  drainage  will 
be  discussed  later,  and  is  introduced  here  to  suggest  the  surgical  im- 
portance of  a  knowledge  of  the  variations  in  the  ducts,  variations 
which  seem  clear  in  their  origin  and  in  their  diversity  when  we  think 
of  the  manner  in  which  the  ducts  change  in  the  course  of  development. 

Two  important  surgical  possibilities  also  depend  upon  the  em- 
bryological  development  of  the  pancreas,  annular  pancreas,  and  ac- 
cessory glands.  If  we  assume  that  the  ventral  bud,  before  it  becomes 
fused  with  the  dorsal  Anlage  (Fig.  6),  becomes  turned  once  around 
the  duodenum  in  the  course  of  the  turning  movements  followed  by 
the  stomach  before  the  stomach  reaches  its  final  position,  and  then 
fuses  with  the  portion  developing  from  the  dorsal  Anlage,  we  have  a 
clear  picture  of  the  manner  in  which  such  a  pancreas  as  is  shown  in 
Fig.  8  could  arise.18  While  very  rare,  this  annular  pancreas  may,  by 
the  production  of  intestinal  obstruction,  be  the  cause  for  surgical 
interference. 

The  occurrence  of  an  accessory  or  aberrant  pancreas  is  explained 
by  Broman  19  on  the  basis  of  the  phylogenetic  development  of  the 
pancreas.  He  assumes  as  the  earliest  type  of  pancreas  one  in  which 
many  small  glands  are  disseminated  in  the  wall  of  the  entire  small 
intestine;  as  the  pancreatic  function,  going  upward  in  the  scale,  be- 
comes more  or  less  dependent  upon  the  liver  function,  we  find  those 
glands  nearest  the  liver  taking  on  the  entire  function,  and  then  unit- 


Fig.  5. 


Diagrammatic  presentation  of  the  relations  of  the  pancreas  to  the  neighboring  organs. 


Fig.  6. 


Reconstruction  of  the  two  pancreas  anlagen  in  a  human  embryo  of  five  weeks.     (From  Hamburger.) 
Ch,  ductus  choledochus;  v,  ventral  anlage;  dr,  dorsal  anlage;  s,  stomach. 


Fig.  7. 


The  four  types  of  anastomosis  between  ductus  choledochus  and  duct  of  Wirsung,  seen  in  cross- 
section  of  the  duodenal  wall.     (From  Letulle  and  Nattan-Larrier.) 

Fig.  8. 


Annular  pancreas.      (From  Cords.)     Ch,  ductus  choledochus;  D,  duct  of  the  dorsal 
V,  duct  of  the  ventral  anlage. 


SURGERY    OF    THE    PANCREAS  11 

ing  in  a  definite  single  organ,  while  those  scattered  below  disappear. 
An  accessory  pancreas  would  therefore  represent  an  atavistic  reversion 
to  the  primitive  type.  Whether  this  explanation  covers  the  not  -un- 
common occurrence  of  such  aberrant  pancreas  tissue  in  the  wall  of 
the  stomach,  or  whether  this  tissue  in  the  stomach  may  be  related  to 
the  left  ventral  bud  which  is  supposed  to  disappear,  matters  little 
to  the  surgeon.  He  must  remember  that  such  glands  do  occur,  in 
the  stomach  wall  or  at  any  point  in  the  wall  of  the  entire  small  in- 
testine, or  even  in  relation  with  the  umbilicus,  and  should  not  mistake 
them  for  neoplasms ;  such  aberrant  organs  may  also  become  diseased, 
independently  of  the  main  organ. 

THE   PHYSIOLOGY 

A  study  of  the  physiology  of  the  pancreas  leads  to  the  conclusion 
that  the  pancreas  is  a  complete,  self-contained  laboratory  of  physio- 
logical chemistry.  Perhaps  this  is  another  reason  why  the  surgeon 
hesitates  to  approach  the  pancreas.  The  development  of  modern 
surgery  daily  makes  clearer  the  fact  that  physiology  is  of  basic  im- 
portance to  surgery,  and  it  is  just  this  organ,  the  pancreas,  which 
demonstrates  that  a  knowledge  of  physiology  is  often  of  more  funda- 
mental importance  than  a  knowledge  of  anatomy:  anatomy  teaches 
only  the  "  how,"  never  the  "  when,"  of  pathology  or  the  "  why  "  of 
physiology.  Further,  the  manner  of  attacking  any  form  of  pan- 
creatic disease  is,  I  believe,  to  be  determined  by  a  knowledge  of 
certain  of  its  physiological  peculiarities. 

Like  all  the  abdominal  organs,  the  pancreas  receives  fibres  from 
the  central  nervous  system  by  two  paths,  the  vagus  and  the  splanchnic. 
The  meaning  of  this  dual  nerve  supply,  and  even  the  relation  of  the 
nervous  system  to  the  activity  of  the  gland,  is  not  yet  clear.  The  role 
of  the  nerve  relations  in  pancreatic  activity  is  further  complicated 
by  the  presence  in  the  gland  of  the  autonomous  nervous  system  repre- 
sented by  the  numerous  ganglia  scattered  throughout  the  gland;  a 
still  further  complication  is  offered  by  the  fact  that  the  most  potent 
stimulant  of  pancreatic  activity  is  not  nerve  stimulation,  but  the 
action  of  a  chemical  stimulant,  brought  to  the  cells  of  the  gland  by 
the  blood  stream  from  its  place  of  origin  in  the  intestinal  mucosa. 

This  substance,  called  "  secretin  "  by  its  discoverers,  Bayliss  and 
Starling,20  and  further  classed  as  a  hormone,  or  chemical  messenger, 


12  INTERNATIONAL    CLINICS 

is  formed  by  the  action  of  hydrochloric  acid  upon  a  substance  called 
"  prosecretin,"  contained  in  the  cells  of  the  mucosa  of  the  duodenum 
and  the  entire  jejunum.  When  secretin  is  brought  to  the  pancreas 
by  the  blood  stream,  the  pancreas  immediately  begins  to  secrete. 
The  normal  process  of  pancreatic  activity  is,  then,  that  the  hydro- 
chloric acid,  coming  from  the  stomach  in  small  amounts  as  the  pylorus 
allows  the  food  to  enter  the  duodenum,  changes  the  prosecretin  into 
secretin,  which  is  carried  to  the  pancreas  and  causes  that  organ  to 
furnish  the  digestive  fluid  necessary  to  complete  the  work  of  digestion 
begun  by  the  ferments  of  the  stomach.  The  creation  of  abnormal 
conditions  by  performing  a  gastroenterostomy,  with  closure  of  the 
pylorus,  does  not  seem  to  seriously  interfere  with  this  relation  of  acid, 
prosecretin,  secretin,  and  pancreatic  juice,  probably  because  the  pro- 
secretin is  found  throughout  the  greater  part  of  the  mucosa  of  the 
small  intestine,  and  the  abnormal  condition  created  by  the  gastro- 
enterostomy is  quickly  compensated.  Alkalies  hinder  the  production 
of  pancreatic  juice,  perhaps  by  neutralizing  the  acid  of  the  gastric 
juice ;  the  use  of  alkalies  is  suggested  to  lessen  the  flow  of  juice  from 
a  fistula  of  the  pancreatic  ducts.  Physiologists  reckon  the  amount  of 
pancreatic  juice  secreted  daily  as  about  equal  to  the  amount  of 
gastric  secretion,  or  in  man  about  1500  ccm. 

The  most  important  constituents  of  the  pancreatic  juice  are  the 
ferments,  or,  better,  the  proferments  or  zymogens.  These  ferments 
are  the  proteolytic  trypsin,  which  breaks  down  the  proteins  to  the 
amino-acids;  a  lipase  or  steapsin,  which  transforms  neutral  fats  into 
fatty  acids  and  glycerin ;  a  rennin-like  ferment ;  a  diastase  or  ptyalin, 
the  same  as  found  in  the  saliva;  a  maltase,  which  can  transform  the 
maltose,  derived  from  the  starch  by  the  diastase,  into  glucose;  a 
lactase  is  found  in  the  pancreas  of  sucklings  and  in  the  pancreas  of 
animals  fed  on  milk-sugar. 

The  pancreatic  juice  contains,  further,  a  nuclease,  which  dissolves 
the  nucleins  which  have  been  precipitated  in  the  stomach ;  the  action 
of  this  ferment  consists  in  transforming  the  gelatinizing  nucleic  acid  a 
into  the  more  soluble,  non-gelatinizing  nucleic  acid  b.  This  fact  of 
digestion  of  the  nucleins  by  the  pancreatic  juice  is  the  basis  for 
Schmidt's  test 21  for  pancreatic  function ;  he  concludes,  from  the 
appearance  of  cell  nuclei  in  the  faeces,  that  a  disturbance  of  pancreatic 
function  exists.     The  theoretical  value  of  this  test  is  impaired  by  the 


SURGERY    OF    THE    PANCREAS  13 

work  of  Umber,22  who  found  that  considerable  amounts  of  nucleins 
are  digested  in  the  stomach,  and  by  the  work  of  Gumlich  23  and 
Araki,24  who  showed  that  the  succus  enterieus  can  dissolve  the 
nucleins. 

Aside  from  the  doubtful  value  to  the  surgeon  of  the  nuclease  of 
the  pancreas,  or  its  absence,  as  an  aid  in  diagnosis,  another  of  the 
pancreatic  ferments  furnishes  the  only  positive  diagnostic  factor  in 
certain  types  of  pancreatic  disease,  in  regard  to  which  factor  there  is 
universal  agreement,  that  it  gives  a  positive,  unfailing  diagnostic  sign. 

This  is  the  lipase  or  steapsin.  To  be  sure,  it  is  necessary  to  per- 
form a  laparotomy  in  order  to  obtain  the  help  of  this  agent  in  diag- 
nosis ;  but  in  the  present  stage  of  our  knowledge  it  would  seem  entirely 
justifiable  to  proceed  to  an  exploratory  laparotomy  and  obtain  the 
advantage  of  an  early  operation  rather  than  wait  for  other  and  by  no 
means  satisfactory  methods  of  diagnosis. 

The  steapsin  of  the  pancreatic  juice  breaks  down  the  neutral  fats 
into  fatty  acids  and  glycerin ;  this  process  occurs,  of  course,  normally 
within  the  intestine,  but  if  the  pancreatic  juice  escapes  into  the  peri- 
toneum or  into  the  tissues  it  can  act  upon  the  fat  of  the  body  itself, 
forming  characteristic,  round,  dead  white  patches,  which,  once  seen, 
are  never  mistaken  for  any  other  condition  (Fig.  14).  The  rela- 
tion of  these  areas  of  fat  necrosis  to  steapsin  was  shown  by  Flexner, 
who  demonstrated  the  ferment  and  its  products  in  these  areas.  This 
fat-splitting  ferment  is  not  contained  in  the  pancreas  as  such,  but  as  a 
zymogen,  steapsinogen,  which  is  transformed  into  the  ferment  steapsin 
by  some  constituent  of  the  bile.  There  seems  to  be  a  certain  amount 
of  active  steapsin  in  the  pancreas,  from  which  we  must  conclude  that 
the  steapsinogen  can  be  activated  by  some  other  substance  than  the 
activator  contained  in  the  bile.  The  occurrence  of  fat  necrosis  would 
not,  therefore,  necessarily  justify  the  conclusion  that  the  bile  had 
been  forced  into  the  pancreatic  ducts,  and  had  there  converted  the 
zymogen  into  the  active  ferment  before  its  escape  into  the  tissues; 
the  theory  would  suggest  such  a  possibility,  but  there  are  no  reports 
from  which  any  deductions  bearing  upon  this  point  can  be  drawn. 

While  the  presence  of  fat  necrosis  is  the  only  positive  sign  of 
pancreatic  disease,  outside  the  pancreas  itself,  it  is  not  necessarily 
always  present. 

The  proteolytic  ferment  of  the  pancreas,  trypsin,  is  the  product 


14  INTERNATIONAL    CLINICS 

all-important  to  the  surgeon,  determining  not  only  the  condition  for 
which  he  must  most  often  approach  the  pancreas,  but,  further,  this 
trypsin  determines  the  manner  in  which,  as  we  shall  see  later,  he 
must  modify  his  treatment,  as  compared  with  his  treatment  of  the 
inflammations  of  other  organs. 

Out  of  the  wealth  of  fact  concerning  trypsin  and  its  relation  to 
digestion  certain  things  stand  forth  which  the  surgeon  must  know; 
to  these  we  will  limit  our  attention.  The  ferment  is  not  contained 
as  a  ferment,  neither  in  the  gland-cells  nor  in  the  ducts,  but  is  found 
in  the  form  of  the  inactive  proferment  or  zymogen,  trypsinogen.  This 
is  the  answer  to  the  old  question  of  why  the  pancreas  does  not  digest 
itself.  The  normal  activating  factor  for  trypsinogen,  the  agent  which 
makes  of  the  harmless  trypsinogen  the  powerful  proteolytic  ferment 
trypsin,  is  produced  exclusively,  under  normal  conditions,  by  the  cells 
of  the  mucosa  of  the  small  intestine,  and  is  called  enterokinase.  This 
body,  concerning  the  relation  of  which  or  its  mode  of  action  little  is 
known,  is  not  continually  secreted  by  the  cells  of  the  intestinal  wall, 
but  only  when  trypsin  (respectively  trypsinogen)  is  brought  into  the 
lumen  of  the  intestine.  The  change  from  trypsinogen  to  trypsin  is 
effected  instantaneously  at  body  temperature. 

This  enterokinase  seems  to  be  the  only  substance  normally  present 
in  the  body  which  can  change  trypsinogen  into  trypsin.  Delezenne  25 
believed  that  an  active  enterokinase  could  be  extracted  from  the  leuco- 
cytes of  the  blood  or  the  Peyer's  plaques  of  the  intestine,  but  this  does 
not  seem  to  be  the  case.  Bayliss  and  Starling  26  state  that  no  other 
substance  can  effect  this  conversion  of  trypsinogen  into  trypsin,  a 
statement  which,  I  think,  we  shall  find  later  should  be  modified — that 
no  other  normal  constituent  of  the  body  can  effect  this  change.  An 
activating  substance  similar  in  action  to  enterokinase,  if  not  identical 
with  it,  appears  to  occur  in  many  bacteria  (Delezenne 25  and 
Hekma  27),  and  there  is  further,  and  surgically  important,  evidence 
that  trypsinogen  is  also  activated  by  some  constituent  of  the  pancreas 
itself  when  the  gland  is  injured  in  such  a  manner  that  necrosis 
develops.  The  observation  was  made  long  ago  by  Heidenhain,28  and 
confirmed  by  others,  that  in  glands  removed  from  the  body  and  in 
watery  extracts  of  glands  trypsin  appears,  at  first  slowly,  then  rather 
rapidly  (Vernon  29). 

The  fact  of  some  such  change  of  trypsinogen  into  trypsin  is  seen 


SURGERY  OF  THE  PANCREAS  15 

in  the  single  experiment  from  which  the  original  of  Fig.  14,  show- 
ing fat  necrosis,  was  obtained.  A  part  of  the  pancreas  of  one  dog, 
removed  under  strict  aseptic  precautions,  was  placed,  again  under 
aseptic  technic,  into  the  peritoneal  cavity  of  another  dog.  The  ensuing 
fat  necrosis  proves  that  the  steapsin  must  have  either  been  present  in 
the  gland  or  else  have  been  activated  from  the  steapsinogen  by  some 
substance  not  normally  present  in  the  gland. 

The  fact  that  such  a  procedure  inevitably  kills  the  dog  into  whose 
belly  the  pancreas  is  placed  shows  that  some  powerful  poison  has  been 
developed,  and,  as  we  shall  see  in  a  later  chapter,  this  is  either  trypsin 
or  the  toxic  products  of  tryptic  digestion. 

On  the  other  hand,  the  injection  of  large  amounts  of  fresh,  normal 
pancreatic  juice  into  the  belly  of  a  dog,  or  the  arranging  of  the  ducts 
of  his  own  pancreas  so  that  they  will  discharge  the  pancreatic  juice 
into  his  own  peritoneal  cavity,  is  followed  by  no  symptoms  at  all. 

The  pancreatic  juice  is  also  said  (Bayliss  and  Starling30)  to 
contain  a  weak  proteolytic  ferment  resembling  erepsin;  this  will 
digest  fresh  fibrin,  but  not  coagulated  protein.  Whether  or  not  this 
proteolytic  ferment  enters  into  the  conditions  which  interest  the 
surgeon  is  not  known. 

THE  INTERNAL  SECRETION  OF  THE  PANCREAS 

The  problem  of  the  internal  secretion  of  the  pancreas,  as  it  is 
called — that  function  which  seems  to  be  at  the  bottom  of  the  meta- 
bolism of  the  carbohydrates — represents,  so  far  as  we  know  at  present, 
the  one  vital  function  of  the  pancreas.  A  whole  library  3  *  has  grown 
out  of  the  study  of  this  function,  and,  judging  from  current  physio- 
logic and  physiologic  chemical  literature,  interest  in  the  problem  is 
as  keen  as  ever,  or  as  ever  since  the  fact  of  the  relation  of  the  pancreas 
to  diabetes  mellitus  was  first  established  by  Minkowski.  A  complete 
discussion  of  this  problem  would  obviously  be  out  of  place  in  this 
surgical  essay,  for,  while  it  is  true  that  the  surgeon  must  know  all 
that  the  internist  knows,  and  then  more — this  more  being  the  whole 
subject  of  surgical  diagnosis  and  technic — yet  it  is  hardly  necessary 
that  the  surgeon  should  be  expected  to  follow  the  painstaking  and 
painful  mental  gyrations  by  which  the  true  internist  finally  success- 
fully arrives  at  the  conclusion  that  our  knowledge  is  limited. 

So  in  regard  to  this  problem  of  the  relation  of  the  pancreas  to 


16 


INTERNATIONAL    CLINICS 


diabetes  mellitus,  let  us  confine  ourselves  to  a  statement  of  what  seems 
to  be  the  consensus  of  opinion.  The  physiologist  and  the  physiological 
chemist  agree  that  the  complete  removal  of  the  pancreas  is  certainly 
followed  by  the  most  severe  form  of  fatal  diabetes :  some  blame  this 
condition  upon  the  loss  of  the  islands  of  Langerhans ;  others  are  not 
so  sure,  since  cases  of  diabetes  mellitus  have  been  recorded  in  which 
no  demonstrable  lesions  of  the  pancreas  could  be  found. 

Most  chemists  are  agreed  that  the  pancreas  furnishes  in  its  in- 
ternal secretion  a  substance  which  facilitates  the  combustion  of  the 
carbohydrates ;  possibly  this  substance  activates  a  glycolytic  or  glucose- 
burning  ferment  produced  by  the  muscles.  The  characteristic  feature 
of  pancreatic  diabetes,  according  to  some  physiological  chemists,  is 
not  the  glucosuria,  but  the  accompanying  evidence  of  a  disturbance 
of  fat  metabolism,  as  manifested  by  the  acidosis ;  therefore  the  finding 
in  the  urine  characteristic  of  pancreatic  disease  would  not  be  glucose, 
but  glucose  plus  acidosis.  In  other  words,  according  to  this  idea, 
glucose  may  appear  in  the  urine  as  a  result,  or  accompaniment,  of 
many  other  conditions  besides  pancreatic  disease ;  acidosis  may  accom- 
pany other  conditions,  such  as  starvation,  but  glucosuria  plus  acidosis 
means  pancreatic  disturbance.  I  trespass  upon  the  peculiar  province 
of  the  internist  to  the  above  extent,  in  order  to  point  out  that  the 
discovery  of  sugar  in  the  urine  is  not  enough  to  justify  the  diagnosis 
of  pancreatic  disease. 

A  matter  of  general  theoretical  interest,  and  of  practical  surgical 
interest,  in  connection  with  the  problem  of  the  internal  function  of 
the  pancreas,  is  the  question  of  the  increased  susceptibility  of  the 
diabetic  to  infection.  It  is  sometimes  taught  that  this  increased 
susceptibility  is  due  to  an  increased  sugar  content  of  the  tissues ;  this, 
however,  cannot  be  the  explanation,  since  the  characteristic  fact  con- 
cerning diabetes  is  that  the  blood  sugar  is  only  slightly  increased :  as 
soon  as  an  increase  occurs  the  sugar  is  carried  off  by  the  kidneys,  and 
hence  the  glucosuria. 

My  first  work  in  connection  with  the  pancreas  concerned  just 
this  point;  it  was  found32  that  there  is  a  considerable  loss  of  hsemo- 
lytic  complement  from  the  serum  of  the  completely  depancreatized 
dog;  this  loss  of  complement — the  finding  having  been  later  con- 
firmed for  the  bacteriolytic  complement  of  the  blood — offers  a  reason- 
able explanation  of  this  diminished  resistance  to  infection,  even  though 
the  mechanism  of  this  loss  of  complement  remains  unexplained. 


SURGERY  OF  THE  PANCREAS  17 

THE  RELATIONS  OF  THE  PANCREAS  TO  THE  OTHER  ORGANS  WITH 
INTERNAL  SECRETION 

What  shall  be  said  of  the  relations  between  the  pancreas  and  the 
other  organs  with  an  internal  secretion  ?  Here  again  we  are  con- 
fronted by  an  extensive  array  of  publications,  from  which  more  than 
the  technical  ability  of  the  most  skilful  surgeon  is  required  to  dissect 
out  the  vital  portion.  I  am  therefore  inclined  to  present  simply  the 
facts  which  I  have  personally  observed;  the  bearing  of  these  facts 
and  their  interrelations  are  not  clear,  nor  is  there,  in  my  opinion, 
sufficient  evidence  to-day  to  permit  of  anything  but  the  most  vague 
theorizing. 

The  first  interrelation  which  has  come  to  my  personal  observation 
is  that  the  suprarenal  exercises  some  sort  of  control  over  the  pancreas. 
Such  an  interrelation  has  been  found  by  others,  partly  on  the  basis 

Fig.  9. 

Respirations  Artificial  respirations, 

I      ■ 


.Pressure  here  much  lower,  than  alter 
first  secretin  when  juice  flowed 
although  now  juice  is  inhibited 


8lood-pressure 


Flow  after  secretin 


|  5cc  adrenalin 


'  iTime  jn* 


The  inhibitory  effect  upon  the  activity  of  the  pancreas,  induced  by  secretin,  of  an  injection  of 

adrenalin. 

of  experiment,  partly  on  the  basis  of  theoretical  labor ;  it  has  even 
been  claimed  that  the  removal  of  the  adrenals  prevents  the  appear- 
ance of  the  glucosuria  following  upon  the  complete  removal  of  the 
pancreas.  The  observations  which  lead  us  to  the  conclusion  that  the 
suprarenals  and  the  pancreas  are  interrelated  are  seen  in  the  accom- 
panying tracings.33  These  tracings  were  obtained  as  follows:  A  dog 
under  constant  ether  anaesthesia  was  attached  to  a  kymograph,  by 
which  was  recorded,  for  the  entire  time  of  the  experiment,  a  con- 
tinuous tracing  of  respiration,  blood-pressure,  with  the  time  in  seconds 
and  a  base  line  on  which  the  flow  of  juice  from  the  pancreas  could 
be  electrically  recorded,  each  vertical  stroke  on  the  base  line  recording 
the  passing  by  the  column  of  juice  of  the  graduations  on  a  cannula 
inserted  in  the  main  pancreatic  duct. 

As  is  shown  by  the  tracing  (Fig.  9),  the  injection  of  5  ccm. 


18  INTERNATIONAL    CLINICS 

of  secretin  caused  a  flow  of  pancreatic  juice,  and  the  injection  of 
5  ccm.  of  adrenalin  stopped  this  flow  within  three  minutes. 

The  converse  of  this  proposition  is  also  true:  i.e.,  that  the  re- 
moval of  the  adrenals  is  followed,  after  a  time,  by  a  flow  of  pancreatic 
juice.  This  is  seen  in  the  tracings  (Figs.  10  and  11),  which  were 
prepared  in  the  same  manner  as  just  described,  by  the  use  of  a  con- 
tinuous kymograph.  In  Fig.  10  A,  a  marked  flow  from  the  pancreas 
is  recorded;  in  Fig.  10,  B,  taken  from  a  later  period  of  the  trac- 
ing, as  shown  by  the  lowered  blood-pressure,  the  flow  has  become 

Fig.  10. 
A 


Cannula  full 
31  35  .  90 


i .     .. Cannula  full  .Emptied  to  20 

Cannula  emptied  to  division  22  "1  I 

!<■    .  .  .  ■  . |  JO         20 


B 

The  induction  of  pancreatic  activity  by  the  removal  of  the  adrenals.  A.  The  flow  at  a  time 
when  blood-pressure  is  still  fairly  high.  B.  The  flow  at  a  later  period,  when  the  blood-pressure  has 
become  much  lower.  The  upper  line  in  each  tracing  is  the  respiratory  tracing;  the  second  line  is 
the  blood-pressure;  on  the  base  line  is  the  record  of  flow  from  the  pancreas,  through  a  graduated 
cannula;  below  is  the  time  in  seconds. 

much  more  marked;  in  Fig.  11  is  shown  the  composite  picture 
of  the  effect  upon  blood-pressure  and  pancreatic  activity,  a  trac- 
ing formed  of  sections  of  the  entire  tracing  taken  at  consecutive 
hourly  intervals ;  in  this  tracing  is  seen  the  effect  upon  the  general 
blood-pressure  of  the  removal  of  the  adrenals,  the  gradual  progressive 
fall,  and  the  appearance  of  the  flow  of  pancreatic  juice.  This  find- 
ing of  some  sort  of  interrelation  between  the  suprarenals  and  the 
pancreas  is,  in  my  opinion,  of  surgical  significance.  It  has  been  shown 
beyond  question  by  the  physiologists  that  the  suprarenals  are  con- 


SURGERY  OF  THE  PANCREAS 


19 


cerned  in  the  formation  of  a  substance,  adrenalin,  which  is  essential 
to  the  maintenance  of  normal  blood-pressure.34  The  proof  of  an 
interrelation  between  pancreas  and  adrenals  raises  the  question  of 
whether  the  collapse  and  fall  of  blood-pressure  so  characteristic  of 
acute  pancreatic  disease  may  not  be  due  to  a  destruction  of  suprarenal 
function.  I  have  as  yet  insufficient  evidence  to  constitute  proof,  only 
sufficient  to  warrant  the  suspicion  that  the  adrenals  are  concerned  in 
acute  pancreatitis. 

The  second  interrelation  which  I  have  observed  is  between  the 
pituitary  and  the  pancreas.35  After  the  removal  of  the  pituitary  from 
dogs,  the  pancreas  has  always,  in  a  long  series  of  experiments,  been 
found  at  autopsy  to  have  a  peculiar  color ;  namely,  that  of  the  normal 


Fig.  11. 


ti    A.M 


Tic 


S  ■"»-*> 


ll( 


*1 


The  effect  upon  blood-pressure  and  the  secretion  of  pancreatic  juice  of  the  removal  of  the 
adrenals.  Ine  pancreatic  secretion  is  shown  by  a  series  of  vertical  marks  on  the  base  line,  each 
mark  recording  the  instant  at  which  the  column  of  juice  passed  the  graduations  of  a  glass  cannula 
connected  with  the  duct. 

gland  during  digestion.  This  pigmentation  of  the  normal  gland 
during  digestion  is  something  apart  from  the  blood  supply,  since  it 
persists  after  washing  the  organ  free  from  blood. 

The  clinical  fact  that  in  certain  cases  of  pituitary  disease  an  in- 
creased sugar  tolerance  can  be  demonstrated  is  interpreted  by  Cush- 
ing  36  as  pointing  to  the  relation  between  pituitary  and  pancreas.  The 
difficulties  encountered  in  attempting  to  perform  satisfactory  experi- 
ments on  sugar  tolerance,  the  complexity  of  the  problem  of  glucose 
metabolism,  together  with  the  natural  dependence  of  glucose  meta- 
bolism upon  carbohydrate  digestion  and  resorption,  have  prevented 
reaching  a  conclusion  perfectly  satisfactory.  Work  upon  this  phase 
of  the  problem  has  been  in  progress  in  my  laboratory  for  some  time, 


20  INTERNATIONAL    CLINICS 

in  collaboration  with  Dr.  A.  I.  Ringer,  but  we  have  as  yet  not 
been  able  to  disentangle  the  numerous  complexities.  Some  relation 
between  pituitary  and  pancreas  certainly  exists. 

The  third  interrelation  which  I  have  observed  is  one  between 
the  pancreas  and  the  spleen.  Schiff,  in  1862,  observed  that  the  spleen 
swells  during  digestion.  Herzen  37  and  Gachet  and  Pachon  38  claim 
that  the  spleen  forms  a  product  of  internal  secretion  which  can 
change  trypsinogen  into  trypsin.  My  contribution  to  the  question  of 
the  interrelation  between  spleen  and  pancreas  is  illustrated  in  Fig.  12, 
which  shows  the  remarkable  atrophy  of  the  spleen  following  the 
complete  removal  of  the  external  function  of  the  pancreas. 

In  other  words,  if  that  part  of  the  pancreas  of  the  dog  be  removed 
which  lies  along  the  duodenum,  tying  off  the  body  and  tail  and  the 
uncinate  process  and  leaving  them  in  the  peritoneal  cavity  so  that  the 
internal  function  of  the  pancreas  is  amply  provided  for,  this  marked 
atrophy  of  the  spleen,  among  other  things,  occurs.  The  change 
apparently  consists  in  a  simple  atrophy,  as  is  shown  in  the  photo- 
micrograph, Fig.  13.  This  splenic  atrophy  has  been  a  constant 
finding  in  a  large  series,  and  has  been  marked  after  three  days'  time. 
The  possible  surgical  bearing  of  this  relation  between  pancreas  and 
spleen  is  suggested  by  the  report  of  Musser,39  of  an  acute  anaemia  in 
four  of  eight  cases  of  acute  pancreatitis.  The  well-known  relation 
of  the  spleen  to  the  blood,  together  with  this  finding  of  acute  splenic 
atrophy,  suggests  an  explanation  of  Musser's  report  of  acute  anaemia, 
and  further  suggests  the  importance  of  clinically  following  the  blood- 
picture  in  cases  of  suspected  or  proved  acute  pancreatitis. 

The  fourth  interrelation  which  has  come  to  my  observation  is 
that  between  the  pancreas  and  the  thyroids.  Fig.  12  shows  the 
results  upon  the  thyroid  gland  of  the  operation  just  described,  of 
the  removal  of  the  external  function  of  the  pancreas.  The  thyroids 
have  in  every  case  of  this  series  shown  a  change  which  consists  in  a 
striking  translucency  or  transparency  of  the  gland;  this  apparently 
depends  upon  a  great  increase  in  colloid,  though  the  alveolar  cells  do 
not  seem  much  changed  microscopically.  In  the  plate  this  peculiar 
transparency  is  illustrated  by  drawing  the  lobe  of  the  thyroid  held 
against  the  light,  with  the  blade  of  a  scalpel  interposed.  The  para- 
thyroids stand  out  against  this  translucent  background  as  delicate 
pink  bodies,  and  even  the  lower  pair  of  parathyroids,  which  in  the 


Fig.  12. 


The  effect  upon  the  spleen  of  the  complete  removal  of  the  external  function  of  the  pancreas. 
The  large  spleen  is  drawn  from  the  measurements  taken  at  the  operation;  the  small  spleen  is  the 
actual  size  of  the  spleen  found  at  autopsy.  Above,  a  normal  thyroid  lobe  of  the  dog;  beside  it,  a 
thyroid  lobe  from  the  dog  whose  spleen  is  pictured. 


SURGERY  OF  THE  PANCREAS  21 

dog  are  buried  within  the  thyroid  tissue,  can  be  seen  on  holding  the 
transparent  thyroid  to  the  light,  while  normally  the  parathyroid  thus 
buried  can  be  found  only  by  cutting  and  staining  serial  sections. 
Microscopically  the  parathyroids  show  no  change. 

'Now  what  do  these  findings  mean,  and  what  is  their  bearing, 
physiological  or  surgical  ?  I  do  not  know,  and  I  do  not  think  that  any- 
body else  knows.  The  only  conclusion  which  I  feel  justified  in  draw- 
ing is  that  the  activity  of  the  pancreas,  as  represented  by  its  relation 
to  the  digestion  and  the  absorption  of  food  by  the  external  secretion, 
together  with  its  further  influence  on  metabolism  by  its  internal 
secretion  or  secretions,  makes  of  the  pancreas  the  mainspring  which 
determines  the  movements  of  every  one  of  the  wheels  in  the  complex 
mechanism  of  the  living  body. 

PANCREASVERGIFTUNG 

On  December  4,  1914,  the  pancreas  was  removed  from  a  normal 
dog  and  dropped  into  the  peritoneal  cavity  of  another  normal  dog, 
the  entire  procedure  being  conducted  under  strict  aseptic  precautions. 
Twenty-four  hours  later  the  animal  was  dead.  The  autopsy,  per- 
formed immediately  after  death,  showed  a  picture  of  beginning  peri- 
tonitis, localized  to  the  peritoneum  which  was  in  immediate  contact 
with  the  softened,  dirty  yellow,  disintegrating  transplanted  pancreas ; 
the  animal's  own  pancreas  was  normal.  Only  one  small  area  of  fat 
necrosis  could  be  found,  this  being  in  the  immediate  proximity  of 
the  transplanted  pancreas.  On  the  other  hand,  the  peritoneal  cavity 
contained  a  considerable  amount  of  dark  fluid,  best  described  as  a 
dirty  fluid,  which,  in  my  experience,  is  always  suggestive  of  pancreatic 
disease,  even  if  not  quite  as  definitely  pathognomonic  as  the  finding  of 
fat  necrosis.  This  acutely  fatal  poisoning  inevitably  follows  the  plac- 
ing of  sterile  pancreatic  tissue,  in  sufficient  amounts,  into  the  peri- 
toneal cavity  of  a  normal  animal,  whether  it  be  the  animal's  own 
tissue,  isolated  from  its  blood  supply  so  that  autolysis  or  necrosis  must 
follow,  or  whether  the  pancreatic  tissue  come  from  another  animal  of 
the  same  species  or  of  a  different  species. 

This  is  the  condition  called  Pancreasvergiftung  by  the  Germans, 
and  it  seems  to  me  that  a  study  of  this  condition  will  place  the  prob- 
lem of  acute  pancreatitis  before  the  surgeon  in  a  different  light  from 
that  which  is  shed  upon  the  subject  by  the  ordinary  text-book  treat- 


22  INTERNATIONAL    CLINICS 

ment,  or  even,  indeed,  by  some  of  the  best  monographs  upon  the 
subject  of  the  surgery  of  the  pancreas. 

Thus  Moynihan,  in  the  supplementary  volume  of  "  Keen's 
System"  (1913),  confines  his  discussion  of  this  subject  to  the  fol- 
lowing words :  "  This  infection,  or  entry  of  intestinal  juice  into  the 
ducts  of  the  pancreas,  activates  the  pancreatic  juice  and  leads  to 
autolysis  of  the  cells  and  gangrene  and  hemorrhage  (Coenen)."  And 
Korte 40  devotes  but  five  lines  to  the  discussion  of  the  work  of 
Doberauer  41  and  of  von  Bergmann  and  Guleke,42  a  manner  of  treat- 
ment which  hardly  does  justice  to  the  subject. 

There  is,  however,  abundant  evidence43  that  this  activation  of 
pancreatic  juice  is  not  only  what  "  leads  to  autolysis  of  the  cells," 
etc.,  but  it  is  just  this  activated  pancreatic  juice  which  is  responsible 
for  the  entire  picture,  canvas  and  frame,  glass  and  signature,  of  this 
most  acute  and  terrible  intoxication,  the  whole  secret  of  acute  pan- 
creatitis. A  full  understanding  of  this  fact  settles  many  of  the 
apparent  problems  of  the  pathology  and  surgery  of  the  pancreas ; 
chronic  pancreatitis  is  an  infectious  condition,  in  which  infection 
alone  is  the  factor;  acute  pancreatitis  is  the  condition,  whether  pri- 
marily traumatic  or  infectious,  in  which  the  necessary  conditions  for 
the  activation  of  pancreatic  juice  have  been  met.  No  further  sub- 
division is  necessary,  nor  can  be  made,  since  the  various  classifications 
of  acute  pancreatitis  become  but  different  degrees  of  the  same  process. 
The  problem  of  the  time  of  operation  becomes  clear — the  sooner  the 
better;  the  question  of  drainage  ceases  to  be  a  question,  a  drainage 
must  be  provided,  not  only  of  the  infection  present  but  of  this  activated 
pancreatic  secretion ;  and  we  must  consider  this  same  type  of  drainage 
when  dealing  with  a  trauma  of  the  pancreas. 

The  problem  of  the  toxic  action  of  the  pancreas  has  not  proved 
easy  of  solution,  nor  is  this  strange,  in  view  of  the  complex  nature  and 
properties  of  the  pancreatic  activities;  not  only  are  many  powerful 
ferments  elaborated  by  the  gland,  but  their  activity  depends  upon  the 
collaboration  of  other  factors — the  activation  of  the  proferments  into 
ferments.  Therefore  it  has  taken  the  combined  efforts  of  many 
workers  to  follow  the  intricacies  of  the  problem,  and  only  by  the  com- 
parative study  of  their  results  can  we  reach  a  definite  conclusion.  The 
discoverer  of  the  pathological  condition  of  fat  necrosis,  Balser,  as 
shown  by  the  title  of  his  paper,44  "  Ueber  Fettnekrose,  eine  zuweilen 


Fig.  13. 


'lfZ^?,***0»r 


-;:t* 


Photomicrograph  of  a  section  of  the  spleen  after  complete  removal  of  the  external  function 
of  the  pancreas.  The  simple  atrophy  of  the  cellular  elements  results  in  a  shrinking  and  consequent 
thickening  of  the  capsule  and  trabecular. 


SUEGERY  OF  THE  PANCREAS  23 

todliche  Krankheit  des  Menschen,"  inclined  to  the  belief  that  the  fat 
necrosis  represented  the  fatal  element  in  acute  pancreatic  disturbance. 
But  that  the  fat  necrosis  is  simply  an  accompanying  symptom,  which 
takes  more  time  for  its  development  than  the  fatal  element  in  the 
process  (Fig.  14),  and  may  therefore  fail  to  appear,  is  shown 
in  the  experiment  described  at  the  beginning  of  this  chapter,  or  in 
the  following  case  reports : 

Case  of  Kirste,4*  1902. — A  man  of  fifty  years  is  seized,  without  prodromal 
symptoms,  with  very  severe  abdominal  pain,  vomiting,  belching,  and  weakness. 
Temperature  normal,  pulse  small  and  rapid.  Death  occurs  after  twenty  hours. 
The  abdomen  contains  a  half  litre  of  blood-stained  fluid;  peritonitis;  necrotic  in- 
fection with  hemorrhage  in  over  one-third  of  the  pancreas. 

Case  of  Heinecke,4"  1907. — A  man  of  thirty-six  years  fell  beneath  a  loaded 
wagon.  Immediate  symptoms  of  peritonitis.  Operation  two  days  later,  prognosis 
serious;  small  amount  of  blood  found  in  the  peritoneal  cavity,  the  intestines  dis- 
tended and  inflamed;  some  tears  in  the  mesentery  are  found  and  repaired,  but  no 
other  injuries  are  seen. 

Death  from  shock  occurs  a  few  hours  after  operation.  Autopsy  shows  frac- 
ture of  several  ribs,  with  blood  in  the  left  pleural  cavity;  hematoma  of  the 
bursa  omentalis;  pancreas  torn  clear  across,  splenic  vessels  not  injured;  dirty 
gray  color  of  the  edges  of  the  pancreas,  as  though  digested;  extensive  diffuse  fat 
necroses. 

Two  cases  reported  before  the  New  York  Surgical  Society  by  Erdman48  il- 
lustrate the  relation  of  fat  necrosis  to  pancreatitis.  The  first  case  was  a  man  ot 
fifty  years,  who,  after  a  history  of  gall-bladder  disease  dating  back  three  years, 
had  a  sudden  attack  of  sharp  pain,  with  profound  jaundice  and  some  cyanosis 
and  dyspnoea.  He  was  operated  on  the  third  day  of  the  attack;  hemorrhagic 
pancreatitis  with  fat  necrosis  was  found.  Recovery  followed  cholecystectomy  and 
choledochotomy. 

The  second  case  was  a  man  of  thirty-five  years,  who  gave  a  history  of  very 
sharp  abdominal  pain,  temperature  102°,  pulse  120.  On  opening  the  abdomen  for 
a  supposed  appendicitis,  free  fluid  was  found.  A  median  incision  was  then  made 
higher  up,  and  an  acute  pancreatitis,  without  any  evidence  of  fat  necrosis,  was 
found.  Liberal  drainage  of  the  pancreas  by  puncture  and  a  cholecystostomy  was 
performed. 

The  direct  experimental  proof  that  the  factor  causing  the  fat 
necrosis  is  not  the  fatal  factor  has  been  offered  by  Lattes,49  who  shows 
that  an  activated  pancreatic  juice  which  exhibits  no  fat-splitting 
power  may  produce  the  typical  fatal  picture  without  the  fat  necrosis ; 
and,  on  the  contrary,  that  an  animal  which  has  developed  no  symp- 
toms following  the  injection  of  an  inactive  pancreatic  juice  may 
show  extensive  fat  necrosis. 

The  factor  which  causes  fat  necrosis  is,  then,  not  the  factor  respon- 


24  INTERNATIONAL    CLINICS 

sible  for  the  fatal  course  of  Pancreasvergiftung;  fat  necrosis,  if  pres- 
ent, is  a  sure  sign  of  pancreatic  disturbance,  but  pancreatic  disturb- 
ance, even  to  the  point  of  producing  a  fatal  result,  may  occur  with  no 
sign  of  fat  necrosis. 

Even  after  having  ruled  out  the  fat-splitting  ferment  as  a  vital 
factor,  the  problem  has  become  only  partly  simplified.  This  fatal 
pancreas  poisoning  can  be  experimentally  produced  by  a  great  variety 
of  procedures,  besides  that  of  placing  sterile  pancreas  tissue  into  the 
peritoneal  cavity:  artificial  ischsemia  (Blume,50  Oser,51  Milisch,52 
Lewit,53  Wolf54);  the  injection  into  the  ducts  of  the  pancreas  of 
various  substances  [oil  (Oser,51  Hess,55  Guleke,56  Eppinger57),  bile 
(Guleke,56  Flexner,58  Opie,59  Oser,51  Polya60),  hydrochloric  acid 
and  intestinal  secretion  (Hlava,61  Flexner  and  Pearce,62  Hildebrand,63 
Rosenbach64),  intestinal  secretion  and  pancreatic  juice,  commercial 
trypsin,  calcium  and  sodium  chloride  (Polya  60),  papain  (Carnot  65), 
adrenalin  (Rosenbach64),  zinc  chloride  (Thirolaix,66  Oser51),  nitric 
acid,  chromic  acid,  formalin,  soda  (Flexner  58)]  ;  or  by  injection  into 
the  blood-vessels  of  substances  such  as  oil,  paraffin,  wax,  lycopodium 
(Panum,67  Lepine,68  Bunge,69  Guleke56) ;  by  tying  off  all  the  ducts 
during  digestion  (Hess55),  or  by  mass  ligatures  and  gross  injury  of 
the  pancreas  (Katz  and  Winkler70). 

This  entire  line  of  experiment  has  one  common  factor,  the  injury 
to  the  pancreas  which  naturally  follows  any  disturbance  of  its  blood 
supply,  and  also  follows  the  injection  of  any  material  into  the  ducts. 
The  pancreas  is  a  very  delicate  and  sensitive  organ  (Pawlow  71),  and 
the  injection  of  any  substance  into  the  ducts  must  be  followed  by 
injury  to  the  finer  branchings  of  the  duct  system,  especially  if,  as  in 
the  majority  of  the  experiments  cited,  the  substance  injected  is  in 
itself  caustic  or  irritating.  The  entire  list  may  therefore  be  boiled 
down  to  the  statement  that  injury  to  the  pancreas,  no  matter  how 
caused,  may  result  in  the  production  of  the  typical  picture  of  Pan- 
creasvergiftung. 

The  injection  into  the  peritoneal  cavity  or  into  the  veins  of  an 
animal  of  inactive  pancreatic  juice  (i.e.,  pancreatic  juice  which  does 
not  show  in  the  test-tube  the  power  of  digesting  proteins)  does  not 
produce  any  symptoms,  except  possibly  a  transitory  lowering  of 
blood-pressure,  a  phenomenon  common  to  the  extracts  of  practically 
all  glandular  structures.    A  similar  injection  of  pancreatic  juice  plus 


¥ 


!.?mi 


Experimental  fat  necrosis  in  the  omentum  of  the  dog.     Found  four  days  after  placing  about  one- 
third  of  a  sterile  normal  pancreas  into  the  belly  of  a  normal  dog. 


SURGERY  OF  THE  PANCREAS  25 

succus  entericus  (i.e.,  a  pancreatic  juice  in  which  the  trypsinogen 
has  been  transformed  into  trypsin  by  the  normal  action  of  the 
enterokinase  of  the  succus  entericus)  will  cause  the  typical  symptoms 
of  pancreas  poisoning  and  death,  the  same  result  in  every  way  as  that 
produced  by  placing  sterile  pancreatic  tissue  into  the  peritoneal  cavity. 
This  fact  is  established  by  the  work  of  Lombroso,72  Roger  and 
Gamier,73  Falloise,74  Cybulski  and  Tartschanow,75  Roger  and 
Gamier,76  Fleig,77  Seidel,78  and  Kirschheim.79  On  the  other  hand, 
Schittenhelm  and  Weichardt,80  and  Fragoin  and  Stradiotti  81  claim 
that  the  injection  of  active  juice  produces  no  symptoms.  From  my 
own  experiments,  I  agree  with  the  majority  opinion ;  active  pancreatic 
juice  is  toxic,  inactive  juice  is  non-toxic,  and  it  has  been  my  further 
experience  that  juice  obtained  under  different  conditions  and  from 
different  animals  may  not  act  in  the  same  manner. 

In  the  estimation  of  such  experiments  it  is  well  to  bear  in  mind 
that  Pawlow  71  has  shown  that  the  ferment  content  of  the  pancreas 
varies  with  the  diet ;  the  most  striking  example  of  this  is  the  fact  that 
a  lactase  is  found  only  in  the  pancreatic  juice  of  sucklings  and  of 
animals  which  have  been  fed  on  milk-sugar.  Further,  it  has  been 
observed  clinically  that  injuries  occurring  to  the  pancreas  during 
digestion  are  more  serious  than  injuries  during  fasting. 

No  other  hypothesis  than  this  of  the  activation  of  pancreatic 
juice  seems  to  explain  such  facts  as  the  following:  If  the  ducts  of 
the  pancreas  be  so  arranged  that  the  pancreatic  juice  flows  out  into 
the  peritoneal  cavity,  no  symptoms  follow;  but  if  the  enterokinase 
containing  intestinal  secretion  be  injected  into  the  peritoneal  cavity 
of  such  an  animal  whose  pancreas  is  discharging  into  his  peritoneal 
cavity,  death  with  the  typical  picture  results ;  while  a  control  experi- 
ment with  the  intestinal  secretion  alone  produces  no  symptoms 
(Lattes  49).  The  rate  of  formation  of  the  toxic  products  also  seems 
to  enter  into  the  problem.  Thus  Maragiiano  82  shows  that  a  pancreas 
ground  to  a  fine  pulp  can  be  placed  in  the  peritoneal  cavity  without 
producing  toxic  symptoms;  whereas  the  introduction  of  this  same 
amount  of  pulp,  together  with  oil,  into  the  peritoneal  cavity  does 
produce  fatal  results.  I  would  explain  this  result  by  the  experiments 
reported  from  my  laboratory,  which  show  that  the  leucocytes  of  the 
peritoneal  cavity  are  inhibited  in  their  normal  work  of  phagocytosis 
and  severely  injured,  if  not  killed,  by  the  presence  of  oil.    Maragli- 


26  INTERNATIONAL    CLINICS 

ano's  results  are  therefore  to  be  explained  by  the  rapid  phagocytosis 
of  the  finely-divided  pancreas,  which  process  is  prevented  by  injuring 
the  phagocytes  with  oil.  In  the  first  instance,  the  pancreas  tissue  is 
removed  by  the  leucocytes  before  it  has  autolyzed  and  activated  the 
proferment ;  in  the  second  instance,  the  inhibition  of  phagocytosis 
permits  this  activation  to  take  place. 

This  leads  us,  without  entering  further  into  the  discussion  of 
many  of  the  factors  involved,  such  as  the  role  played  by  the  weak, 
active,  proteolytic  ferment  of  fresh  pancreatic  juice  which  was  de- 
scribed by  Bayliss  and  Starling,30  to  the  question  of  main  surgical 
importance:  Can  the  pancreatic  secretion  be  rendered  toxic  by  the 
substances  arising  from  autolysis  \  This  particular  question  seems 
to  find  its  answer — an  affirmative  one — most  clearly  in  the  work  of 
Lattes.49  Lattes  finds  that  there  is  a  substance  in  the  autolyzed 
pancreas  (that  is,  in  a  pancreas  which  has  been  left  outside  the  body 
for  a  time  until  the  disintegration  of  the  cells  known  as  autolysis,  or 
self  solution,  has  begun)  which  has  the  power  of  activating  fresh 
pancreatic  juice,  or,  as  he  prefers  to  consider  the  process,  which  has 
the  power  of  greatly  increasing  the  proteolytic  activity  of  the  juice. 
This  activating  substance  is  more  stable  toward  heat  than  the  proteo- 
lytic ferment,  and  can  be  obtained  free  from  ferment  by  heating 
autolyzed  pancreas  to  60°  C.  for  fifteen  minutes.  Such  an  extract, 
added  to  pancreatic  juice,  produces  fatal  results;  such  an  extract, 
heated  to  75°  C.  for  fifteen  minutes — a  procedure  which  destroys 
this  activating  substance — added  to  pancreatic  juice,  produces  no 
symptoms. 

It  hardly  interests  the  surgeon  to  enter  into  further  details  of  the 
discussion,  such  as  the  question  of  whether  the  necrosis  activates  the 
juice,  or  the  activated  juice  causes  the  necrosis ;  of  whether  the  toxic 
action  is  a  property  of  the  pancreatic  secretion  itself,  or  if  the  toxicity 
is  the  expression  of  the  toxic  properties  of  the  products  of  the  first 
cleavage  of  the  proteins  of  the  body  by  the  pancreatic  secretion.  The 
fact  stands  clear,  that  an  activated  pancreatic  secretion,  set  free  in 
the  body,  either  activated  by  enterokinase  in  the  normal  manner,  as 
the  surgeon  might  find  in  a  case  of  coincident  injury  of  pancreas  and 
intestine,  or  activated  by  a  substance  produced  by  the  necrosis  (re- 
spectively autolysis)  of  the  gland,  causes  the  fatal  symptoms  of  acute 
pancreatitis.     The  further  question  of  whether  bacteria  can  activate 


SURGERY  OF  THE  PANCREAS  27 

the  juice  or  not  seems  almost  secondary,  when  the  fact  that  the  gland- 
tissue  can,  on  necrosis,  produce  an  activating  factor  is  established; 
the  surgeon  knows  too  well  that  bacteria  can  cause  a  necrosis. 

THE  RELATION  OF  THE  PANCREAS  TO  HIGH  INTESTINAL  OBSTRUCTION 

The  clinical  similarity  between  acute  pancreatitis  and  high  in- 
testinal obstruction  has  led  me  to  the  conclusion  that  this  similarity 
of  symptoms  may  depend  upon  the  fact  that  the  symptoms  in  both 
instances  are  due  to  the  same  underlying  cause;  i.e.,  the  absorption 
into  the  body  of  activated  pancreatic  juice.83  I  am  aware  that  this 
suggestion  seems  contradicted  by  practically  all  the  experimental 
work  which  has  been  done;  all  other  workers  seem  to  feel  that  they 
have  excluded  the  pancreas  as  a  source  of  the  fatal  poison  in  high 
intestinal  obstruction,  even  though  they  fail  utterly  to  agree  as  to 
the  source  and  nature  of  the  poison.  There  are  numerous  reasons 
why  I  am  convinced  that  none  of  these  experiments  has  necessarily 
ruled  out  the  pancreas  as  the  source  of  the  toxin.  A  discussion  of  the 
long  line  of  experimentation  which  has  led  me  to  this  conclusion 
would,  however,  lead  us  too  far  from  our  subject,  and  so  I  shall 
mention  but  one  series  of  experiments,  which,  I  think,  confirms  my 
belief. 

If  a  closed  loop  of  the  lower  ileum  be  made  in  a  dog,  by  cutting 
the  gut  at  two  places  about  ten  inches  apart,  closing  in  both  ends  of 
this  segment,  and  restoring  the  continuity  of  the  intestinal  tract  by 
an  end-to-end  anastomosis  of  the  upper  and  lower  ends  of  the  ileum, 
the  animal  will  live  for  months  with  no  disturbance  of  health.  This 
was  first  proved  by  Halstead,84  many  years  ago.  If  now  this  same 
operation  be  repeated,  with  the  single  exception  that  25  ccm.  of  nor- 
mal pancreatic  juice  be  placed  in  this  isolated  loop  of  ileum,  the  dog 
will  die  with  the  typical  symptoms  of  high  intestinal  obstruction. 

This  experiment,  which  has  often  succeeded,  although  it  may  fail 
if  the  pancreatic  juice  is  not  really  active  juice,  is  sufficient  proof,  to 
my  mind,  of  the  relation  between  the  pancreas  and  high  intestinal 
obstruction.  In  short,  the  symptoms  of  high  intestinal  obstruction 
are  the  symptoms  of  Pancreasvergiftung. 

I  introduce  this  relation  of  the  pancreas  at  this  time  for  two 
reasons :  First,  to  point  out  the  extent  of  the  relation  of  the  pancreas 
to  surgery ;  and,  second,  because  a  further  consideration  of  this  ques- 


28  INTERNATIONAL    CLINICS 

tion  points  the  way  in  which  these  symptoms  of  pancreas  poisoning — 
shock  and  fatal  intoxication — may  be  treated  until  an  operation  shall 
have  removed  the  cause.  Hartwell  and  Hoguet 85  believe  as  a  result 
of  their  experiments  on  high  obstruction  that  the  cause  of  death  is 
the  dehydration  of  the  tissues  consequent  upon  the  excessive  loss  of 
water  from  the  body  by  vomiting.  This  point  of  view  is,  to  my  mind, 
untenable,  because  of  the  clinical  fact  that  not  all  experimental 
animals  nor  all  patients  lose  fluid  in  excessive  amounts;  vomiting  is 
not  always  present  to  such  excess.  However,  acting  on  their  theory, 
they  found  the  highly  important  fact  that  a  dog  which  would  ordinarily 
die  about  eighty-four  hours  after  the  production  of  a  high  obstruction 
could  be  kept  alive  for  so  long  as  twelve  days  by  the  introduction  into 
the  body  of  large  amounts  of  normal  saline  solution.  Therefore,  in 
order  to  combat  the  shock,  which  is  often  so  acute  and  extreme  that 
operation  cannot  be  undertaken,  and  to  aid  in  the  excretion  of  the 
poison,  I  suggest  the  intravenous  introduction  of  normal  saline;  be- 
cause, whether  we  agree  that  the  poison  in  the  two  conditions  is  one 
and  the  same,  or  whether  we  disagree,  the  saline  infusion  would 
mechanically  raise  blood-pressure  and  aid  elimination. 

Because  of  the  relation  pointed  out  above  between  the  adrenals 
and  the  pancreas,  I  would  further  suggest  the  addition  of  small 
amounts  of  adrenalin,  continuously  administered  in  dilution  in  the 
saline  solution,  before,  during,  and,  if  needful,  after  the  operation 
for  the  relief  of  the  obstruction  or  for  the  drainage  of  the  acutely 
inflamed  pancreas. 

THE  PATHOLOGY  OF  THE  PANCREAS 

There  are  two  methods  which  may  be  followed  in  presenting  the 
subject  of  the  pathology  of  a  given  organ:  To  review  the  subject  as 
though  the  whole  of  pathology  were  founded  upon  the  findings  in  that 
organ,  entering  into  a  discussion  of  the  numbers  of  cases  of  this  or 
that  which  have  been  reported,  with  particular  importance  granted 
not  to  the  common  conditions  but  to  the  rare  anomalies.  This  seems 
to  be  a  favorite  pastime  of  the  so-called  "  clinical  pathologists,"  yet  it 
is  only  in  so  far  as  the  rare  case  explains  the  common  case  that  such 
pastime  becomes  anything  more  than  harmless.  The  other  method  is 
to  treat  the  pathology  of  an  organ  as  a  chapter  of  general  pathology ; 
to  consider,  from  the  point  of  view  of  the  fundamental  laws  of  gen- 


SURGERY  OF  THE  PANCREAS  29 

eral  pathology,  what  processes  might  be  expected  to  occur  in  a  given 
organ,  and  to  add  only  those  special  lesions  which  depend  upon  the 
anatomical  or  physiological  peculiarities  of  that  organ. 

This  latter  method  is  the  one  that  appeals  to  me;  just  as  the 
developmental  anomalies  of  an  organ  depend  upon  the  embryology  of 
that  organ,  so  its  pathology  depends  upon  the  peculiarities  of  struct- 
ure, function,  and  location,  and  a  knowledge  of  these  peculiarities  leads 
the  surgeon  not  only  to  a  proper  concept  of  the  pathology  but  also  of 
the  surgery.  Surgery  in  the  broad  sense  must  accomplish  not  only 
the  removal  of  disease  but  also  the  restoration  of  normal  function. 

The  pancreas  is  liable  to  developmental  anomalies,  both  of  loca- 
tion— accessory  pancreas;  of  external  form, — annular  pancreas,  the 
one  of  chief  surgical  interest — and  of  the  arrangement  of  its  ducts, 
all  of  which  were  discussed  under  the  heading  of  "  Embryology." 

It  may  be  abnormally  small — hypoplasia ;  since  it  seems  to  vary  so 
much  in  size,  an  hypertrophic  development  has  not  been  recorded. 
The  pancreas  is  a  glandular  organ  of  enterodermic  origin ;  it  is  there- 
fore subject  to  all  the  ills  to  which  the  glandular  structures  derived 
from  the  entoderm  are  liable ;  it  has  an  external  function  in  the  form 
of  a  secreted  fluid,  and  is  therefore  subject  to  the  formation  of  cysts. 
Since  the  dangerous  factor  peculiar  to  the  pancreatic  secretion,  the 
powerful  protein  digesting  agent,  trypsin,  is  harmless  until  trans- 
formed from  its  harmless  zymogen  stage  by  the  action  of  a  substance 
formed  in  but  two  ways — normally,  outside  the  pancreas,  in  the  wall 
of  the  intestine;  abnormally,  inside  the  pancreas,  by  the  autolysis  of 
the  substance  of  the  gland  itself — these  cysts  do  not  digest  their  walls, 
although  they  may  do  so  if  inflammation,  with  consequent  autolysis 
and  activation  of  the  trypsinogen,  occurs.  Since  this  secretion  is 
highly  alkaline  because  of  the  presence  of  alkaline  salts,  we  may 
expect,  under  conditions  of  retention  of  the  secretion,  that  a  precipita- 
tion of  these  salts  may  result  in  the  formation  of  calculi,  just  as  in  the 
salivary  glands,  the  kidneys,  or  the  bile-passages.  The  conditions 
favoring  this  precipitation  are  doubtless  the  same  in  all  locations; 
they  seem  to  depend  upon  the  presence  in  the  stagnant  secretion  of 
bacteria  which  by  their  action  start  the  precipitation  of  the  salts 
about  them.  The  so-called  pseudocyst  of  the  pancreas  is  a  misleading 
term;  by  it  is  meant  a  collection  of  fluid  in  the  lesser  omental  sac, 
which  fluid  contains  pancreatic  products. 


30  INTERNATIONAL    CLINICS 

Since  the  pancreas  has  blood-vessels,  hemorrhage  may  occur  into 
it;  since  it  has  lymphatics  which  are  in  direct  communication  with 
the  lymphatics  of  neighboring  organs,  infection  and  metastasizing 
tumors  may  pass  from  it  to  neighboring  organs,  and  from  neighboring 
organs  to  it.  Since  all  of  its  blood  drains  into  the  portal  vein,  the 
pancreas  must  share  in  the  passive  congestion  consequent  upon  portal 
interference;  it  is  normally  hypersemic  during  digestion.  Tubercu- 
losis is  rare,  congenital  syphilis  not  so  rare ;  a  general  fatty  infiltra- 
tion occurs  as  in  other  parenchymatous  organs,  and,  with  them,  the 
pancreas  shares  in  amyloid  degeneration.  Tumors  may  be  expected ; 
adenomas,  cystadenomas,  carcinomas ;  sarcoma  is  rare.  The  arrange- 
ment of  the  lymphatics,  previously  discussed,  explains  fully  why 
primary  tumors  of  neighboring  organs  metastasize  so  readily  into  the 
pancreas,  and  likewise  why  neighboring  organs  are  conversely  so 
readily  involved  in  primary  pancreatic  malignancy. 

The  surgical  interest  in  the  inflammatory  processes  in  the  pancreas 
justifies  a  separate  and  more  extended  treatment. 

PANCREATITIS 

Before  attempting  a  classification  of  pancreatitis,  we  must  be  sure 
that  all  the  factors  involved  are  clearly  before  us,  and  that  their 
interaction  is  definitely  understood.  Thus  Deaver  and  Pf  eiff  er  86 
finally  arrive  at  a  correct  conclusion,  but  by  a  process  including  some 
decidedly  incorrect  reasoning,  when  they  write :  "  It  is  not  beyond 
the  range  of  probability  that  certain  cases  of  hemorrhagic  pancreatitis 
may  be  initiated  by  infection  reaching  the  pancreas  through  the  lymph- 
channels.  It  is  certain  that  not  all  hemorrhagic  pancreatitis  is  pro- 
duced by  the  lodgement  of  a  gall-stone  in  the  papilla  of  Vater,  causing 
retro jection  of  the  bile  into  the  pancreatic  duct.  A  fair  percentage  of 
such  cases  are  not  accompanied  by  gall-stones.  Neither  is  it  necessary 
that  duodenal  contents  be  regurgitated  into  the  pancreatic  duct  in  order 
that  activation  of  the  retained  pancreatic  ferments  may  occur.  The 
hormone  secretion  arriving  by  the  blood  stimulates  the  secretion  of 
pancreatic  juice.  Activation  of  the  juice  within  the  gland  is  not 
necessary  to  its  digestive  action,  as  the  clinical  observations  of  fat 
necrosis  and  the  postmortem  autodigestion  of  the  gland  will  attest. 
With  infection  of  the  gland,  obstruction  of  the  ducts  by  a  resulting 
engorgement,  and  stimulation  of  the  active  pancreatic  secretion  by 


SURGERY  OF  THE  PANCREAS  31 

hormone  action  we  have  all  the  conditions  necessary  for  focal  necrosis 
of  the  pancreas,  erosion  of  the  blood-vessels,  diffuse  hemorrhage,  fol- 
lowed by  extensive  gangrene  and  suppuration." 

Now  activation  of  juice  within  the  gland  is  not  necessary  to  its 
digestive  action  upon  fats,  as  the  clinical  observations  of  fat  necrosis 
show,  and  as  is  shown  by  the  experimental  work  upon  fat  necrosis; 
the  fat-splitting  ferment  steapsin  has  nothing  to  do  with  the  protein- 
digesting  ferment  trypsin,  and  so  fat  necrosis  proves  nothing  in  regard 
to  protein  digestion.  The  fact  that  the  gland  does  not  digest  itself 
during  life,  but  that  digestion  does  set  in  very  soon  after  death,  attests 
the  fact  that  the  death  of  the  cells  of  the  pancreas  sets  free  a  factor 
which  can  activate  the  tripsinogen.  With  infection  of  the  gland, 
obstruction  of  the  ducts  by  a  resulting  engorgement  is  not  necessary, 
since  infection  may  cause  the  death  of  the  cells  which  sets  free  the 
activating  factor.  Stimulation  of  the  active  pancreatic  secretion  by 
hormone  ation  is  not  necessary,  since  trypsinogen  is  preformed  in 
the  acinar  cells  and  is  not  formed  at  the  moment  of  excretion  from 
the  cell ;  the  post-mortem  digestion  of  the  gland  will  attest  this  fact. 

With  infection  of  the  gland  alone  we  have  all  the  conditions 
necessary  for  necrosis  and  consequent  activation  of  the  trypsinogen 
into  trypsin,  with  the  result  of  erosion  of  the  blood-vessels  and  local 
hemorrhage,  perhaps ;  or  diffuse  hemorrhage,  perhaps ;  or  extensive 
gangrene,  perhaps ;  or  we  may  have  infection  without  activation  of 
proferment,  and  therefore  only  suppuration. 

The  autopsy  in  vivo  doubtless  supersedes  the  old-style  pathology 
in  the  study  of  the  pancreas,  since  the  gland  is  subject  to  such  rapid 
and  extensive  postmortem  or  even  antemortem  change;  experimental 
pathology  supersedes  the  autopsy  in  vivo,  since  all  the  conditions  can 
here  be  controlled,  pathogenesis  as  well  as  time  and  extent  of  an 
autopsy  in  vivo  or  of  a  postmortem. 

So  as  Deaver's  autopsy  in  vivo  leads  him  to  the  conclusion  that 
pancreatitis,  chronic  and  acute,  may  be  the  result  of  infection,  the 
study  and  analysis  of  the  experimental  results  in  physiology  and 
pathology  which  I  have  endeavored  to  present  in  these  pages  lead  to 
the  conclusion  that  Deaver's  surmise  is  undoubtedly  correct. 

Chronic  pancreatitis  is  the  result  of  an  infection  of  the  interlobular 
connective  tissue  of  the  pancreas,  therefore  it  is  a  lymphangitis. 

Acute  pancreatitis  is  the  result  of  the  setting  free  into  the  sur- 


32  INTERNATIONAL    CLINICS 

rounding  tissues  of  trypsinogen  from  the  gland-cells  and  the  trans- 
formation of  this  trypsinogen  into  trypsin  by  one  of  two  factors — 
either  enterokinase,  as  may  happen  rarely  in  coincident  injury  of 
pancreas  and  intestine,  or  by  an  activating  substance  produced  when 
the  gland  itself  undergoes  autolysis.  This  proteolytic  enzyme  can 
digest  the  living  proteid  of  all  the  structures  with  which  it  comes  in 
contact.  Since  the  pancreas  is  richly  supplied  with  blood-vessels, 
they  are  digested  along  with  the  rest  of  the  gland,  and  hemorrhage, 
either  localized  or  diffuse,  is  commonly  a  marked  accompaniment  of 
acute  pancreatitis.  Hemorrhage  is  not  an  essential  factor,  as  seen  in 
cases  of  experimental  pancreas  poisoning;  since  the  pancreas  lies  in 
such  close  relation  with  large  veins  and  arteries,  an  extraglandular, 
even  postoperative,  and  very  severe  hemorrhage  may  occur.  This 
setting  free  of  activated  ferment  may  be  brought  about  by  any  factor 
or  combination  of  factors  which  supplies  the  two  necessary  ingredients, 
setting  free  of  proferment  and  of  activator ;  infection,  trauma  of  the 
gland,  either  direct  mechanical  trauma,  or  indirect  trauma,  as  by 
embolism,  for  example,  or  indirect  trauma  caused,  experimentally  at 
least,  by  occlusion  of  the  papilla  of  Vater  and  forcible  injection  of 
bile  into  the  pancreatic  duct. 

Chronic  pancreatitis  =  infection. 

Acute  pancreatitis  =  liberation  of  trypsin,  by  infection  or  trauma. 

The  only  valid  classification  of  infection  is  one  based  on  the 
identification  of  the  specific  microorganism  involved,  as  in  all  other 
pathological  conditions  of  infection.  Now  such  a  classification  is 
almost  ruled  out  with  the  pancreas,  especially  in  acute  pancreatitis, 
since  the  early  peritonitis  of  adjoining  loops  of  intestine  favors  the 
addition  of  microorganisms  from  the  intestinal  tract  to  the  causative 
microorganism.  The  rapid  postmortem  and  even  antemortem  changes 
in  the  pancreas  so  obscure  the  picture  that  the  pathologist  seldom  sees 
the  pancreas  in  the  condition  to  which  the  surgeon's  attention  is  most 
frequently  drawn.  We  therefore  have  the  unusual  condition  in  which 
the  pathologist  is  decidedly  limited;  and  likewise  the  surgeon  is 
limited,  as  Deaver  admits,  when  he  says  he  has  no  definite  informa- 
tion concerning  the  pancreas  in  appendicitis,  not  feeling  justified  in 
extending  his  autopsy  in  vivo  to  the  extent  of  examining  the  upper 
abdomen  as  a  routine  procedure  in  appendicitis. 

The  difficulties  of  the  problem  are  increased  because  of  the  troubles 


SURGERY  OF  THE  PANCREAS  33 

encountered  when  we  attempt  to  compare  the  results  of  one  man's 
findings  with  those  of  another,  it  being  a  matter  of  opinion  rather 
than  demonstrable  fact.  Because  of  this  we  can  do  no  better  than  to 
follow  the  reasoning  advanced  by  Deaver  and  Pfeiffer  in  support  of 
their  conclusion  that  chronic  pancreatitis  is  a  lymphangitis,  and  to 
weigh  their  evidence. 

The  avenues  by  which  infection  may  reach  the  pancreas  are, 
according  to  Deaver  and  Pfeiffer,86  (1)  the  blood  stream,  (2)  the 
ducts,  and  (3)  the  lymphatics.  The  circulation  is  ruled  out  because 
the  diseases  with  which  pancreatitis  is  associated  are  not  character- 
ized by  bacteremia,  nor  is  the  pancreas  often  involved  in  conditions 
of  general  bacteremia.  That  this  mode  of  infection  is  possible  is 
evidenced  by  the  infection  of  the  pancreas  in  miliary  tuberculosis,  in 
syphilis,  and  occasionally  by  abscess  formation  in  pyemia.  In  addi- 
tion to  these  conditions,  I  would  call  the  attention  of  the  reader  to 
the  fact  that  the  blood  supply  of  the  pancreas  is  doubtless  most 
developed  in  connection  with  the  functional  gland  tissue  rather  than 
with  the  interlobular  connective  tissue,  so  that  the  chance  of  localiza- 
tion of  a  blood-borne  infection  would  be  decidedly  in  favor  of  the 
acini  rather  than  the  connective  tissue.  The  characteristic  of  chronic 
pancreatitis  is  an  interlobular  inflammation.  The  lymphatics  form 
an  anastomosing  network  in  this  interlobular  connective  tissue. 

The  ducts  of  the  pancreas,  according  to  Deaver  and  Pfeiffer,  can 
not  be  exonerated  from  all  blame.  The  relation  of  gall-stones  to 
pancreatitis,  especially  to  acute  pancreatitis,  was  clearly  presented  by 
Opie;  but  all  cases  of  pancreatitis,  acute  or  chronic,  are  not  accom- 
panied by  cholelithiasis,  and  trauma  may  present  the  same  picture. 
While  this  manner  of  infection  of  the  pancreas  must  be  admitted, 
Deaver  and  Pfeiffer  think  it  has  been  overworked.  To  their  reason- 
ing, the  logic  of  which  is  undoubtedly  correct,  I  would  add  two  further 
considerations.  The  operation  to  be  described  later  under  the  name 
of  pancreatoenterostomy,  first  devised  by  Coffey  87  and  later  modified 
in  this  laboratory,  demonstrates  that  the  pancreatic  duct  can  be  suc- 
cessfully anastomosed  with  the  intestine  by  simply  cutting  off  the  end 
of  the  pancreas  until  a  fair-sized  duct  is  reached,  and  dropping  this 
cut  end  of  the  pancreas  directly  into  the  lumen  of  the  gut,  then  closing 
the  intestine  around  the  pancreas,  the  normal  duct  openings  having 
been  ligated.     Now  such  an  operation  certainly  does  away  with  the 


34  INTERNATIONAL    CLINICS 

assumed  valve  action  of  the  normal  papilla,  which  is  supposed  to 
protect  the  duct  from  ascending  infection,  yet  the  pancreas  does  not 
become  infected. 

I  would  further  call  attention  in  this  connection  to  the  experi- 
mental results  reported  by  Sweet  and  Stewart 88  on  the  subject  of  the 
ascending  infection  of  the  kidneys.  They  report,  as  a  result  of  a  long 
series  of  experiments,  that  the  lumen  of  the  ureter  must  be  ruled  out 
as  the  pathway  of  the  ascending  infection,  and  that  the  lymphatics 
of  the  bladder,  ureter,  and  kidney  must  be  looked  upon  as  the  route 
followed  by  the  infection.  These  conclusions  were  reached  by  various 
experiments;  they  show  that  if  a  section  of  one  ureter  be  removed 
and  replaced  by  rubber  tubing  tied  into  the  ends  of  the  ureter  and 
the  bladder  be  infected,  with  ligation  of  the  urethra,  the  resultant 
infection  travels  upward  to  the  kidney  on  the  unoperated  side,  but 
only  to  the  rubber  tube  on  the  operated  side.  This  experiment  seems 
to  rule  out  the  lumen  of  the  ureter ;  the  mucosa  of  the  ureter  is  ruled 
out  by  their  final  series  of  experiments,  which  show  that  the  kidney 
pelvis  can  be  directly  anastomosed  with  the  intestine  without  a  result- 
ing infection  of  kidney  pelvis  or  kidney  tissue. 

The  evidence  that  chronic  pancreatitis  is  not  necessarily  associated 
with  infections  of  the  biliary  passages  is  presented  by  Deaver  and 
Pf eiffer  in  the  following  summary  of  the  cases  which  they  have  studied 
since  their  attention  has  been  directed  to  the  lymphatics  as  a  possible 
route  of  infection : 

Number  of  cases  Pancreatitis  present  Percentage 

Cholelithiasis    99  40  40.4 

Cholecystitis      14  9  64.2 

Duodenal   ulcer    16  2  12.5 

Gastric   ulcer    3  1  33.3 

To  this  might  be  added  the  statistical  report  of  Walther-Sallis,89 
of  250  cases  of  chronic  pancreatitis.  He  finds  50  cases  on  record  in 
which  there  were  no  associated  lesions  of  the  biliary  system ;  in  27 
cases  the  entire  gland  was  involved,  in  23  only  the  head;  in  110  cases 
cholelithiasis  was  present,  in  75  other  cases  an  angiocholecystitis ;  in 
15  cases  the  pancreatitis  was  associated  with  an  intestinal  lesion, 
ulcer,  or  cancer. 

The  most  convincing  argument  advanced  by  Deaver  and  Pfeiffer 
in  favor  of  the  lymphatics  is  the  fact  that  in  the  majority  of  cases  of 
chronic  pancreatitis  the  entire  gland  is  not  affected,  as  it  should  be 


SURGERY  OF  THE  PANCREAS  35 

if  the  infection  ascended  the  ducts,  but  only  the  "  triangle  of  pan- 
creatic inflammation,"  which  lies  between  the  duodenum  and  the  con- 
verging ducts  of  Santorini  and  Wirsung,  the  lymphatics  of  which, 
according  to  Franke  (Fig.  4),  can  be  injected  from  the  gall-bladder. 
The  relation  of  the  inflammation  of  the  pancreas  to  gall-bladder  dis- 
ease is  unquestionable.  If  the  pancreas  can  be  infected  through  the 
lymph-paths  connecting  the  gall-bladder  and  pancreas  which  have  been 
demonstrated  by  Franke5  (Fig.  4),  then  the  pancreas  could  be 
infected  from  almost  any  point  in  the  abdomen  through  the  lymphatic 
anastomoses  demonstrated  by  Bartels  3  (Fig.  3). 

Walther-Sallis  finds  90  males  and  160  females  afflicted;  of  the  50 
cases  of  non-biliary  pancreatitis,  16  were  male  and  34  females.  This 
writer  considers  that  pregnancy  has  an  etiological  relationship  to 
chronic  pancreatitis. 

Acute  pancreatitis  presents  another  element  of  trouble  to  the 
solution  of  the  problem  of  pathogenesis;  namely,  the  wiping  out  of 
the  evidences  of  the  primary  causative  factor  by  the  hemorrhage  and 
digestion  of  the  gland.  An  embolus  might  cause  the  primary  de- 
structive changes  in  the  organ,  and  yet  would  itself  be  among  the  first 
structures  to  suffer  digestion.  We  have  already  considered  acute 
pancreatitis  in  fact  under  the  heading  of  "  Pankreasvergiftung  " ;  it 
was  there  sufficiently  emphasized  that  the  only  essential  factor  is  the 
activation  of  the  proteolytic  proferment,  tripsinogen,  which  can  be 
brought  about  by  a  substance  liberated  from  the  gland  on  autolysis. 
JSTordmann  90  has  added  to  the  study  of  his  eight  clinical  cases  an 
experimental  study ;  he  reaches  the  conclusion  above  noted  in  regard 
to  such  experiments,  that  the  injection  of  substances  into  the  pancre- 
atic duct  injures  the  finest  branchings  of  the  ducts  and  consequently 
forces  pancreatic  secretion  into  the  tissues;  this  process,  he  thinks,  is 
not  what  occurs  in  human  pathology.  His  experiments  on  dogs  led 
him  to  the  conclusion  that  for  the  production  of  a  pancreatitis  there 
must  be  a  simultaneous  prevention  of  the  escape  of  bile  and  of  pan- 
creatic juice  into  the  intestine,  with  also  a  coincident  infection  of 
the  bile-passages.  This  point  of  view,  championed  by  Opie  in  his 
classic  work,  seems  to  be  sadly  undermined  by  the  facts  mentioned 
in  the  discussion  of  pancreas  poisoning — that  an  acutely  fatal  pancreas 
poisoning  can  be  produced  by  dropping  a  sterile  pancreas  into  the 
belly  of  a  normal  dog,  and  that  the  same  result  follows  the  separation 


36  INTERNATIONAL    CLINICS 

of  a  portion  of  the  dog's  own  pancreas  from  its  blood  supply ;  whereas 
the  ducts  of  the  pancreas  can  be  ligated  with  no  pancreatitis,  provided 
the  blood  supply  be  unharmed;  but  if  any  amount  of  pancreatic 
tissue  be  included  in  the  ligature  of  the  duct,  a  fatal  pancreatitis  may 
follow  (personal  experiments).  The  clinical  fact  that  numerous  cases 
have  been  reported  of  acute  pancreatitis  following  trauma  to  the 
pancreas  also  proves  that  a  hindrance  to  the  flow  of  pancreatic  juice 
is  not  a  necessary  etiological  factor. 

Arnsperger  91  reports  three  cases  of  acute  pancreatitis  associated 
with  cholelithiasis  and  cholecystitis;  there  were  no  inflammatory 
changes  in  the  bile-passages,  the  pancreatic  ducts,  or  the  duodenum. 
He  believes  that  these  cases,  therefore,  represented  an  infection  of  the 
pancreas  through  the  lymph-channels. 

There  seems  to  be  no  escape  from  the  conclusion  that  the  only 
essential  etiological  factor  in  acute  pancreatitis  is  the  activation  of 
trypsinogen  into  trypsin ;  because 

(1)  IsTo  other  explanation  covers  the  clinical  cases  associated  with 
infection  and  the  clinical  cases  associated  with  traumatism  of  the 
gland. 

(2)  ~No  other  explanation  offers  an  understanding  of  the  fact  that 
injury  to  the  gland  during  digestion  is  more  serious  than  injury  at 
other  times. 

(3)  The  picture  of  an  acute  pancreatitis  can  be  fully  reproduced 
by  placing  the  sterile  pancreas  of  one  normal  dog  into  the  belly  of 
another  normal  dog;  or 

(4)  By  isolating  a  portion  of  the  dog's  own  pancreas  from  its 
blood  supply. 

(5)  The  ducts  of  the  pancreas  can  be  tied  without  causing  any- 
thing except  simple  sclerosis ;  but 

(6)  A  fatal  pancreatitis  may  follow  the  ligation  of  the  ducts,  if 
any  great  amount  of  gland  tissue  is  so  included  in  the  ligature  of  the 
ducts  that  autolysis  occurs  in  the  ligated  bit  of  tissue  (own 
experiment) . 

THE  FACTOR  OF   SAFETY 

Before  proceeding  to  the  removal  of  all  or  any  portion  of  an 
organ  the  surgeon  must  know  whether  that  organ  is  essential  to  life, 
and,  if  so,  whether  the  entire  organ  or  only  a  part,  and  what  part. 
This  factor  of  safety  is  well  understood  in  the  case  of  the  paired 


Fig.  15. 


The  pancreas  of  the  dog,  seen  from  behind.  Ch.,  ductus  choledochus;  TV.,  duct  of  Wirsung;  S., 
duct  of  Santorini;  V.,  island  of  pancreas  developing  from  the  ventral  anlage;  the  normal  line  of 
separation  of  this  island  from  the  main  pancreas  is  marked  by  the  pancreaticoduodenal  vessels, 
normally  covered,  but  here  the  tissue  is  drawn  apart  to  show  the  division  between  the  two  parts 
of  the  pancreas  of  the  dog. 


SURGERY  OF  THE  PANCREAS  37 

organs  of  the  body — at  least  one  entire  half  can  be  done  away  with, 
and  often  more.  It  is  not  understood  by  the  surgeon  just  how  far  he 
might  go  with  the  pancreas.  As  we  have  seen  in  our  discussion  of 
the  physiology  of  the  pancreas,  we  must  recognize  that  the  two  func- 
tions of  the  pancreas  are  entirely  separate :  the  external  function,  con- 
cerned in  the  elaboration  of  the  specific  digestive  ferments,  has  noth- 
ing to  do  with  the  internal  function,  the  one  concerned  with  the 
control  of  glucose  metabolism. 

The  external  function  of  the  pancreas  can  be,  theoretically,  entirely 
dispensed  with.  The  various  digestive  enzymes  are  duplicated  in  so 
many  places  throughout  the  gastro-intestinal  tract  that  the  loss  of  one 
is  not  vital;  surgeons  have  long  known  that  the  digestive  function 
of  the  stomach  is  not  a  necessity.  So  with  the  pancreas,  the  complete 
loss  of  external  pancreatic  function  should  result  only  in  an  inability 
to  care  for  food  in  excessive  amounts  or  unsuitable  quality.  An 
individual  should  therefore  be  able  to  exist  in  comfort  on  a  proper  diet. 

I  confess  that  I  was  unwilling  to  accept  this  teaching  of  the 
physiological  chemist,  and  therefore  performed  a  series  of  experi- 
ments, of  which  the  following  may  serve  as  illustrations : 

On  December  9,  1913,  the  duodenal  portion  and  the  uncinate 
process  of  the  pancreas  of  a  dog  was  removed,  the  body  and  tail  being 
tied  off  (as  at  B,  Fig.  15)  by  a  ligature  including  vessels  and  duct, 
and  dropped  back  into  the  peritoneal  cavity  to  care  for  the  internal 
function  of  the  pancreas.  The  dog  weighed  11  K.  400  g.  The  dog 
recovered  completely  from  the  operation,  and  on  December  17,  1913, 
weighed  11  K.  800  g.  On  January  3,  1914,  the  dog  showed  a  marked 
loss  of  weight,  now  weighing  7  K.  200  g. ;  the  urine  was  examined  on 
this  date  and  contained  no  sugar.  The  stools  showed  the  pronounced 
fatty,  or  fatty-acid,  characteristic  of  the  stools  of  an  animal  with  loss 
of  the  steapsin  of  the  pancreatic  juice ;  stools  very  massive.  On 
March  11,  1914,  the  dog  weighed  6  K.  80  g. ;  April  22,  1914,  6  K. 
560  g.;  May  5,  1914,  6  K.  302  g. ;  May  11,  1914,  6  K.  220  g. ; 
October  4,  1914,  6  K.  220  g.  The  urine  shows  no  sugar  on  this  date. 
The  animal  at  this  time  seemed  perfectly  well,  the  only  clinical  symp- 
tom being  the  loss  of  weight  and  the  typical  stools.  The  animal  was 
killed  on  this  date  for  autopsy.  The  autopsy  shows  two  striking 
changes,  an  extreme  atrophy  of  the  spleen,  the  organ  being  only  about 
one-tenth  size  of  the  normal  spleen  of  a  dog  of  this  size ;  the  thyroids 


38  INTERNATIONAL    CLINICS 

are  very  pale  and  translucent.  The  intestines  show  a  marked  brownish 
pigmentation.     There  is  very  little  fat  in  the  body. 

It  is  interesting  to  note  that  the  weight  remained  practically 
stationary  from  May  to  October,  1914.  This  experiment  is  given 
as  the  type  of  a  large  series  of  similar  experiments,  in  all  of  which 
the  atrophy  of  the  spleen,  the  colloidal  change  in  the  thyroid,  and 
the  loss  of  weight  are  constant,  as  is  also  the  apparent  good  health, 
except  this  loss  of  weight,  of  the  animals  on  the  mixed  diet  fed  to  all 
the  normal  dogs. 

On  November  4,  1914,  the  same  operation  was  performed  on  a 
dog.  The  spleen  measured  16  Cm.  in  length,  with  width  of  head  of 
5  Cm.  and  width  of  tail  of  3  Cm.  (Fig.  12).  The  animal  was 
autopsied  on  December  3,  1914 ;  the  spleen  measured  8  Cm.  in  length, 
with  width  of  head  .of  2.75  Cm.  and  width  of  tail  of  1.75  Cm.  This 
spleen  is  shown  in  natural  size  on  Fig.  12,  the  larger  spleen  beside 
it  being  drawn  from  the  measurements  taken  at  the  operation  on 
November  4,  1914.  The  thyroids  drawn  in  this  plate  (Fig.  12) 
show  the  peculiar  effect  of  this  operation  upon  the  thyroid ;  a  normal 
thyroid  of  the  dog  is  pictured,  and  beside  it  the  pale,  transparent 
thyroid  lobe  from  the  dog  just  described,  the  lobe  being  drawn  as  it 
appears  when  held  toward  the  light,  with  a  scalpel  blade  behind  it  to 
show  the  transparency.  The  parathyroids  of  the  upper  part  of  the 
thyroid  lobe,  which  are  normally  on  the  surface  in  the  dog,  appear  in 
both  lobes ;  the  lower  pair  of  parathyroids  are  normally  buried  in  the 
thyroid  tissue  and  can  only  be  found  by  cutting  serial  sections;  in 
this  peculiarly  transparent  thyroid  the  lower  parathyroid  can  be  seen 
plainly,  on  holding  the  lobe  against  the  light.  Microscopically  the 
thyroid  shows  an  increase  of  colloid,  with  flattening  of  the  alveolar 
cells. 

We  see,  then,  that  the  physiological  chemist  is  right  as  regards 
the  theory  of  digestion ;  he  usually  is.  Two  further  facts,  however, 
stand  out  from  these  experiments  which  make  it  doubtful  if  the 
external  function  of  the  pancreas  can  be  completely  removed,  leaving 
a  small  portion  of  tissue  to  take  care  of  the  glucose  metabolism ;  these 
facts  are  the  extreme  atrophy  of  the  spleen  and  the  changes  in  the 
thyroids.  This  striking  atrophy  of  the  spleen  and  the  speed  with 
which  it  occurs — a  marked  atrophy  occurred  in  one  animal  which 
died  three  days  after  operation  from  acute  pancreatitis — and  the 


SURGERY  OF  THE  PANCREAS  39 

relation  of  the  spleen  to  the  blood-forming  organs,  suggest  a  basis  for 
the  diagnostic  finding  reported  by  Musser39  of  an  acute  anaemia  in 
four  of  eight  cases  of  acute  pancreatitis. 

The  animal  reported  in  the  first  case  above  was  in  good  health  on 
the  ordinary  kennel  diet  at  the  end  of  ten  months,  and  was  killed  in 
order  that  the  changes  occurring  at  the  end  of  that  time  might  be 
studied.  Whatever  the  changes  in  the  thyroid  and  spleen  may  mean, 
they  can  hardly  be  considered  vital.  These  experiments  present  for 
consideration  the  question  of  whether,  in  a  case  of  carcinomatous 
involvement  of  the  greater  part  of  the  pancreas,  the  surgeon  would 
not  be  justified  in  performing  the  extirpation  of  the  entire  gland, 
excepting  a  small  part  of  the  tail  which  is  tied  off  to  care  for  the 
internal  function ;  such  a  patient  should  live  in  comfort  with  dietary 
care,  so  far  as  his  digestive  functions  are  concerned,  and  his  chance 
of  life  would  be  prolonged,  minus  the  external  function  of  the 
pancreas,  as  compared  with  the  certainty  of  death  plus  a  cancer  of 
the  pancreas. 

The  external  secretion  of  the  pancreas  cannot  be  separated  from 
the  internal  function  and  studied  alone.  The  following  experiment 
is  therefore  presented,  since  it  demonstrates  the  extreme  limit  of 
removal  of  pancreas  tissue,  an  extreme  to  which  the  surgeon  would 
doubtless  never  approach,  unless  it  might  be  in  a  case  where  he  should 
choose  the  lesser  of  two  evils. 

I  present  in  Fig.  15  a  drawing  of  the  normal  pancreas  of  the 
dog  as  seen  from  the  posterior  aspect  of  the  stomach  and  duodenum ; 
the  little  island  of  pancreas  tissue,  the  lobe  which  develops  in  the  dog 
from  the  ventral  Anlage  and  contains  the  duct  of  Wirsung,  which  in 
the  dog  remains  the  smaller  duct,  is  shown  slightly  separated  by  blunt 
dissection  from  the  main  part  of  the  gland.  The  ducts  of  the  two 
parts  anastomose  in  one  or  two  places.  This  drawing  is  presented  in 
order  to  visualize  to  the  surgeon,  who  does  not  ordinarily  deal  in 
weights  and  to  whom,  therefore,  the  comparative  weight  of  this  island, 
as  compared  with  the  entire  gland,  would  convey  no  definite  idea,  just 
how  little  of  the  pancreas  is  needed  to  completely  cover  the  nitrogen 
metabolism  of  the  body. 

On  October  9,  1914,  the  pancreas  was  removed  from  a  dog,  No.  71, 
leaving  this  island  with  its  normal  blood  supply  and  its  own  duct. 
The  total  weight  of  the  pancreas,  plus  the  estimated  weight  of  this 


40 


INTERNATIONAL    CLINICS 


island,  was  16.9  g. ;  the  estimated  weight  of  the  portion  left  was 
1.2  g. ;  the  dog  died  December  15,  1914,  and  the  autopsy  showed  a 
portion  of  pancreas  weighing  1.9  g.  Practically  eight-ninths  of  the 
pancreas  was  therefore  removed. 

The  nitrogen  metabolism  of  this  dog  was  studied  in  comparison 

Fig.  16. 


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Reconstruction  in  the  form  of  curves  of  the  tables  showing  the  rate  of  nitrogen  excretion  in  a 
normal  dog.  No.  82,  and  the  rate  of  nitrogen  excretion  in  a  dog  from  which  eight-ninths  of  the  pan- 
creas has  been  removed,  dog  No.  71.  The  curves  show  that  the  results  are  the  same  in  both  instances, 
and  that,  therefore,  the  removal  of  all  but  one-ninth  of  the  pancreas  produces  no  change  in  nitrogen 
metabolism,  neither  in  rate  of  resorption  nor  in  rate  of  excretion. 

with  the  study  of  a  normal  dog.  The  details  of  the  study  of  the 
normal  dog,  ~No.  82,  are  given  in  the  first  of  the  following  tables ;  the 
results  in  the  depancreatized  dog,  No.  71,  in  the  second  table.  The 
results  obtained  from  the  study  of  both  animals  are  presented  in  the 
form  of  curves,  Fig.  16,  from  which  it  is  seen  that  there  are  no 
differences  in  the  rate  of  resorption  or  excretion  of  nitrogen. 


SURGERY    OF    THE    PANCREAS 


41 


Table 

I 

Normal 

Dog 

No.  82 

Date,  1914. 

Time 

Number  of  hours 

Total  nitrogen 

Nitrogen  per 
hour 

November  19 

12 

1.84 

0.153 

20 

12 

1.87 

0.156 

20 

8.50-10.50 

2 

0.346 

0.173 

20 

10.50-12.50 

2 

0.300 

0.150 

20 

12.50-  2.50 

2 

0.313 

0.156 

20 

2.50-  9.05 

6.25 

0.985 

0.157 

20 

9.05-  9.05 

12.0 

1.89 

0.157 

21 

9.05  a.m.* 

21 

9.05-11.05 

2.0 

0.875 

0.437 

21 

11.05-  1.05 

2.0 

1.66 

0.830 

21 

1.05-  2.35 

1.50 

1.21 

0.807 

21 

2.35-  5.05 

2.50 

2.07 

0.829 

21 

5.05-  7.05 

2.00 

1.72 

0.860 

21 

7.05-  9.05 

2.00 

1.62 

0.810 

21 

9.05-  9.05 

12.00 

4.66 

0.388 

22 

9.05-  9.05 

12.00 

2.32 

0.193 

22 

9.05-  9.05 

12.00 

2.49 

0.207 

*  Fed  600  gms.  of  beef-heart=16.8  gms.  of  nitrogen. 

Table  II 


Dog  No. 

11 

Date,  1914. 

Time 

tt               Total 
Hour3    Nitrogen 

Nitrogen 
per  hour 

Total 
glucose 

Glucose  per 
hour 

November  15 

8.57-  8.57 

12.0 

1.27 

0.106 

0.00 

0.00 

15 

8.57-  8.57 

12.0 

1.15 

0.096 

0.00 

0.00 

16 

8.57  a.m.* 

16 

8.57-10.57 

2.0 

0.753 

0.376 

1.61 

0.85 

16 

10.57-12.57 

2.0 

1.67 

0.835 

4.63 

2.315 

16 

12.57-  2.57 

2.0 

1.61 

0.805 

5.02 

2.510 

16 

2.57-  4.57 

2.0 

1.64 

0.82 

6.27 

3.135 

16 

4.57-  8.57 

4.0 

3.07 

0.768 

11.50 

2.875 

16 

8.57-10.57 

2.0 

1.37 

0.685 

4.93 

2.465 

16 

10.57-  8.57 

10.0 

4.40 

0.440 

12.50 

1.25 

17 

8.57-10.57 

2.0 

0.46 

0.230 

0.89 

0.445 

17 

10.57-12.57 

2.0 

0.435 

0.217 

0.26 

0.130 

17 

12.57-  2.57 

2.0 

0.290 

0.145 

0.00 

0.00 

17 

2.57-  8.57 

6.0 

0.780 

0.130 

0.00 

0.00 

17 

8.57-  8.57 

12.0 

1.150 

0.096 

0.00 

0.00 

*  Fed  600  gms.  of  beef-heart=16.8  gms.  of  nitrogen. 


That  portion  of  nitrogen  metabolism  represented  by  the  rate  of 
absorption  and  the  rate  of  excretion  is  therefore  normal  in  an  animal 
which  possesses  only  about  one-ninth  of  the  normal  amount  of  pancreas 


42  INTERNATIONAL    CLINICS 

tissue  (Fig.  16).  A  study  of  Table  II  brings  out  the  fact  that 
the  portion  of  the  protein  molecule  which  is  available  for  transforma- 
tion into  glucose — a  portion  representing  57.6  per  cent,  of  the  entire 
protein  molecule — is  disturbed  in  its  metabolism.  This  is  seen  in  the 
fact  that  this  animal  could  care  for  an  amount  of  protein  represented 
by  a  nitrogen  output  of  about  0.150  gramme,  but  an  increase  over 
this  amount  was  marked  by  the  appearance  of  sugar;  this  was  a 
constant  finding  in  other  experiments  with  this  dog  and  with  other 
similar  dogs,  and  offers  the  experimental  basis  for  the  suggestion 
that  the  study  of  the  glucose  metabolism  is  the  most  promising  of  the 
functional  tests  for  the  diagnosis  of  pancreatic  involvement.  The 
feeding  of  glucose  and  carbohydrates  to  these  animals  shows  that 
there  is  the  same  sharp  line  of  glucose  utilization,  regardless  of 
whether  the  sugar  is  fed  as  such,  or  derived  from  carbohydrates  in 
general,  or  from  protein.  The  disturbance  is  not  of  sugar,  carbo- 
hydrate in  general,  or  of  protein  resorption,  but  of  glucose  utilization. 

The  results  of  these  studies  indicate  that  two-thirds  of  the  pancreas 
at  least  could  be  removed,  and  these  results,  taken  in  conjunction  with 
the  results  of  the  operation  described  as  pancreato-enterostomy,  show 
the  practicability  of  pancreas  resection. 

A  study  of  the  record  of  dog  No.  71  indicates  that  we  have  gone 
beyond  the  limit  of  safety.  Just  how  large  a  piece  of  pancreas  is 
essential  in  order  to  preserve  normal  metabolism  might  be  difficult 
to  determine  and  would  perhaps  vary  with  different  individuals.  In 
the  following  experiment,  dog  No.  84,  roughly  four-fifths  of  the 
pancreas  was  removed.  A  study  of  the  results  shows  that  the  pan- 
creatic control  of  glucose  utilization  increases  out  of  all  proportion 
to  the  relative  increase  of  pancreas  tissue.  Dog  No.  71  was  on  the 
very  threshold  of  sugar  tolerance.  Dog  No.  84  can  tolerate  between 
30  and  40  grammes  of  glucose.  At  the  autopsy  of  dog  No.  71,  1.9 
grammes  of  pancreatic  tissue  were  found ;  the  piece  of  pancreas  left 
in  dog  No.  84  was  estimated  at  operation  to  weigh  about  2.6  grammes. 
Approximately  one-fifth  of  the  pancreas  would  seem,  therefore,  able 
to  care  for  ordinary  metabolic  requirements. 

Dog  No.  84 

December     4,  1914. — Operation   performed.     Pancreas  removed,   13.1   Gms.     Con- 
trol piece,  2.6  +.     Total  size  of  pancreas,  15.7  +. 
December  16,  1914. — 10.30  a.m.,  50  Gms.     Uneeda  biscuit. 


SURGERY  OF  THE  PANCREAS  43 

December  17,  1914. — 8.55  a.m.,  catheterized  and  bladder  washed.  Urine  sugar- 
free. 

December  17,  1914. — 9.30  a.m.,  100  Gms.  of  Uneeda  biscuit. 

December  18,  1914. — 8.  55  a.m.,  catheterized  and  bladder  washed.  Urine  faint  re- 
duction   (pseudo). 

December  18,  1914.— 10.00  a.m.,  600  Gms.  of  beef-heart  fed. 

December  19,  1914. — 3.30  p.m.,  catheterized  and  bladder  washed.  Urine  sugar- 
free. 

December  21,  1914. — 10.30  a.m.,  20  Gms.  of  glucose  in  water  given  per  os. 

December  22,  1914. — 9.00  a.m.,  catheterized  and  bladder  washed.  Urine  sugar- 
free. 

December  22,  1914. — 11.15  a.m.,  30  Gms.  glucose  as  above. 

December  23,  1914. — 8.55  a.m.,  catheterized  and  bladder  washed.  Urine  sugar- 
free. 

December  23,  1914. — 11  a.m.,  600  Gms.  of  beef-heart. 

December  24,  1914. — 8.55  a.m.,  catheterized  and  bladder  washed.    Urine,  no  sugar. 

December  24,  1914. — 9.30  a.m.,  40  Gms.  of  glucose  given  per  os.  Urine  contains 
sugar. 

THE    DIAGNOSIS 

There  are  three  cardinal  signs  in  surgical  diagnosis:  pain,  dis- 
turbance of  form  or  relation,  and  disturbance  of  function.  Applying 
these  to  the  pancreas,  and  bearing  in  mind  the  peculiarities  of  the 
pancreas  which  have  been  described,  we  find  that  we  could  not  expect 
pain  to  be  a  definite  sign  of  pancreatic  involvement,  or,  even  if  it 
were,  pain  could  not  be  localized  to  any  one  point.  The  parenchyma- 
tous organs  of  the  belly  are  not  afflicted  with  sensory  nerves ;  they  are 
protected  by  a  sensory  device,  which  consists  in  the  presence  in  the 
peritoneal  covering  of  these  organs  of  sensory  fibres.  Now  the  head 
of  the  pancreas  is  related  to  the  peritoneum  of  the  duodenum  and  of 
the  transverse  colon,  while  the  tail  may  be  in  relation  with  the  peri- 
toneum of  the  left  kidney  or  the  spleen.  The  pain  of  chronic  pancre- 
atitis is  therefore  found  to  be  of  varying  degree,  perhaps  more  often 
referred  to  the  umbilical  region,  and  increased  on  deep  palpation,  but 
sometimes  occurring  elsewhere  in  the  abdomen ;  often  a  definite  pain 
is  not  complained  of,  but  a  general  discomfort.  Tumors  would  not 
cause  pain  until  they  had  reached  dimensions  which  produced  a  strain 
of  the  overlying  peritoneum.  The  pain  of  an  acute  pancreatitis  is 
essentially  the  pain  of  an  acute  peritonitis  of  the  upper  abdomen, 
and  presents  no  specific  element,  as  compared  with  the  pain  of  high 
obstruction,  or  ruptured  gall-bladder,  or  ruptured  stomach-wall,  unless, 
perhaps,  the  extreme  intensity  of  the  pain  might  be  suggestive  of 


44  INTERNATIONAL    CLINICS 

pancreatitis.92  It  may  be  noted,  in  this  connection,  that  the  injection 
of  active  pancreatic  extracts,  or  of  trypsin,  is  reported  to  be  imme- 
diately provocative  of  severe  pain.43 

Under  the  heading  of  disturbance  of  form  or  relations  we  find 
sometimes  a  more  or  less  definite  mass  in  the  region  of  the  pancreas 
in  chronic  pancreatitis,  and  sometimes,  because  of  a  coincident  or 
causative  cholangitis,  jaundice  and  a  distended  gall-bladder;  theoreti- 
cally, at  least,  the  same  jaundice,  without  history  of  cholangitis  or 
its  accompaniment,  cholelithiasis,  might  be  expected,  since  it  is 
mechanically  possible  for  the  swollen  head  of  the  pancreas  to  compress 
the  common  duct ;  there  seems  to  be  considerable  difference  of  opinion 
as  to  whether  this  actually  occurs  in  fact  or  only  in  theory.  In  regard 
to  cysts  and  tumors,  the  demonstration  of  a  mass  in  the  pancreatic 
region  is  the  only  definite  sign ;  perhaps  this  is  also  true  of  abscesses. 
It  must  be  remembered,  however,  as  shown  in  Fig.  1,  that  such  cysts 
and  tumors  have  no  definite  manner  of  presenting  themselves  as 
regards  the  stomach  and  colon ;  according  to  the  degree  of  gastroptosis 
present,  tumors  of  the  pancreas  may  appear  above  or  below  the 
stomach,  or  below  both  stomach  and  colon ;  an  abscess  of  the  body  of 
the  pancreas  may  creep  along  in  the  retroperitoneal  tissue  and  finally 
present  far  below  the  pancreas. 

A  change  of  the  normal  consistence  of  an  organ  is  a  surgical  sign 
which  belongs  under  the  general  heading  of  disturbance  of  form  or 
relation ;  such  a  change  of  consistence  is,  for  example,  of  importance 
in  the  diagnosis  of  breast  conditions.  A  change  in  the  consistence  of 
the  pancreas,  as  felt  by  the  surgeon  at  operation,  has  often  been  the 
decisive  factor  in  the  diagnosis  of  chronic  pancreatitis,  yet  it  is 
difficult  to  judge  the  value  of  this  sign. 

"  It  should  be  borne  in  mind  that  a  hard  pancreas  is  not  neces- 
sarily a  diseased  pancreas.  I  know  of  cases  in  which  the  diagnosis 
of  chronic  pancreatitis  was  based  on  the  hard  feel  of  the  pancreas  at 
operation,  and  subsequently  at  autopsy  a  normal  pancreas  was  found. 
It  is  a  matter  of  common  knowledge  among  pathologists  that  a  normal 
pancreas  may  have  a  consistence  of  almost  stony  hardness." 

I  do  not  find  that  pathologists  are  quite  ready  to  agree  with 
Pratt's  93  last  sentence;  "  stony  hardness  "  seems  somewhat  hyperbolic. 
Nevertheless,  pathologists  point  out  that  the  pancreas  of  the  normal 
human  being,  because  of  its  structure — extensively  lobulated,  with  a 


SURGERY  OF  THE  PANCREAS  45 

large  relative  amount  of  connective  tissue  extending  in  between  the 
lobules — is  a  firm,  dense  structure  to  the  touch,  and  in  respect  to  this 
tactile  density  or  hardness  is  to  be  placed  next  the  uterus ;  beginners 
in  autopsy  technic  commonly  report  the  normal  pancreas  as  sclerosed 
or  the  site  of  chronic  inflammation,  because  of  this  natural  hardness.94 
For  these  reasons  the  pathologists  have  often  doubted  the  diagnosis 
made  by  the  surgeon  at  the  operating  table,  especially  since  many 
cases  have  been  noted  like  the  one  mentioned  above  by  Pratt,  where  a 
pancreas  pronounced  diseased  by  the  surgeon  was  later  demonstrated 
by  the  pathologist  to  be  normal.  But,  while  the  surgeon  may  not 
appreciate  the  facts  known  to  the  competent  pathologist  concerning 
the  normal  density  of  the  pancreas,  the  pathologist,  on  the  other  hand, 
does  not  seem  to  be  cognizant  of  the  fact  known  to  the  competent 
surgeon,  that  the  gland  is  seldom  uniformly  affected  in  chronic  pancre- 
atitis. This  fact  that  the  lesion  is  normally  localized  to  the  head  of 
the  organ — a  fact  presented  by  Deaver  and  Pfeiffer  as  proof  that 
the  infection  is  not  a  duct-borne  infection — and  that  the  body  and 
tail  are  unaffected,  so  far  as  can  be  ascertained  by  palpation,  makes 
it  seem  doubtful  that  the  surgeon's  sign  of  change  in  consistence  is 
so  fundamentally  an  error.  Deaver  and  Pfeiffer  report  that  in  42 
cases  of  the  series  of  chronic  pancreatitis  under  discussion,  or  42  out 
of  a  total  of  52  cases,  the  head  alone  was  affected ;  in  only  9  was  the 
tail  noted  as  showing  any  change  in  shape,  size,  or  consistence;  in 
27  cases  there  was  well-marked  involvement  of  the  lymph-nodes  in 
the  neighborhood  of  the  head  of  the  pancreas. 

This  common  localization  of  the  disease  process  to  the  "  triangle 
of  pancreatic  inflammation,"  lying  between  the  duodenum  and  the 
converging  ducts  of  Santorini  and  Wirsung,  affords  a  means  by  which 
the  surgeon  can  control  his  own  findings,  and  we  might  conclude  that, 
in  order  to  escape  the  scorn  of  the  pathologist,  the  surgeon  should 
limit  his  definite  diagnosis,  as  based  on  the  consistence  of  the  pancreas, 
to  those  cases  in  which  a  manifest  difference  exists  between  the  differ- 
ent portions  of  the  gland. 

Under  the  heading  of  disturbances  of  function  falls  an  entire 
series  of  tests,  all  of  which  must  be  weighed  with  a  constant  considera- 
tion of  the  facts  which  have  been  mentioned  in  the  foregoing  pages 
concerning  the  normal  physiology  of  the  pancreas,  and  particularly 
the  facts  presented  under  the  heading  of  the  factor  of  safety ;  the  con- 


46  INTERNATIONAL    CLINICS 

sideration  of  the  factor  of  safety,  at  first  sight  a  surgical  considera- 
tion, was  presented  before  this  discussion  of  diagnosis  because  the 
facts  there  related  must  be  borne  in  mind  in  weighing  the  value  of 
any  functional  test. 

The  pancreatic  juice  is  not  secreted  continuously,  even  during 
digestion,  but  only  when  the  hydrochloric  acid  entering  the  duodenum 
causes  the  change  of  prosecretin  into  secretin ;  the  secretin  entering 
the  blood  stream  is  carried  to  the  pancreas  and  incites  the  gland  to 
activity;  but  even  now  the  activity  of  the  pancreatic  juice  is  not 
entirely  unfolded ;  the  steapsin  needs  the  aid  of  the  bile  for  its  com- 
plete effectiveness,  although  it  develops  a  certain  amount  of  activity 
without  the  bile.  The  proteolytic  activity  of  the  pancreatic  juice  is 
developed  by  the  assistance  of  a  further  factor,  the  enterokinase  of 
the  intestinal  mucosa,  which  again  is  not  preformed  in  the  intestinal 
lumen,  but  only  when  trypsinogen  is  present  in  the  intestinal  canal. 

The  function  of  the  pancreas  is  therefore  not  dependent  upon 
the  pancreas  alone,  but  upon  the  successful  collaboration  of  the 
pancreas  with  all  the  other  factors  involved:  the  motor  function  of 
the  stomach;  the  formation  of  hydrochloric  acid;  the  formation  of 
prosecretin  and  the  transformation  of  prosecretin  into  secretin ;  the 
effectiveness  of  the  action  of  this  secretin  upon  the  pancreas;  the 
formation  of  enterokinase  and  its  successful  action  upon  trypsinogen ; 
the  relation  of  the  bile;  and,  finally,  we  must  remember  that  the 
composition  of  the  pancreatic  juice  depends  upon  the  diet  (Paw- 
low71).  Perhaps  even  fundamental  to  these  considerations  is  the 
fact  that  the  factor  of  safety,  surgical  and  physiological,  is  so  high 
that  we  could  hardly  expect  functional  tests  to  give  positive  results 
until  the  disease  process  had  affected  a  large  portion  of  the  gland. 

The  functional  tests  which  have  been  suggested  may  be  divided 
into  four  general  groups : 

1.  Those  showing  a  disturbance  of  the  interrelations  between  the 
pancreas  and  other  organs. 

2.  Those  showing  a  disturbance  of  the  internal  function  of  the 
pancreas  which  is  involved  in  glucosuria. 

3.  Those  showing  the  presence  in  the  stomach  content,  in  the 
urine,  or  the  faeces  of  the  normal  products  of  the  pancreas. 

4.  Those  which  indicate  the  extent  of  pancreatic  function  by  the 


SURGERY  OF  THE  PANCREAS  47 

extent  of  the  digestion  of  those  substances  which  are  supposed  to  be 
digested  by  the  pancreatic  secretion  only. 

Under  the  heading  of  the  tests  showing  a  disturbance  of  the  inter- 
relations between  the  pancreas  and  other  organs  belongs  the  test  sug- 
gested by  Loewi,  the  dilation  of  the  pupil  after  instilling  adrenalin 
into  the  conjunctival  sac.  This  test  is  explained  by  assuming  some 
disturbance  of  the  sympathetic  system,  and  there  is  little  evidence 
which  would  lead  me  to  expect  a  constant  result.  Sailer  95  reports 
one  positive  among  30  cases.  The  fact  that  the  tonus  of  the  sympa- 
thetic system  is  maintained,  in  some  degree  at  least,  by  the  adrenals, 
and  the  facts  of  the  interrelations  between  the  pancreas  and  the 
adrenals  which  have  been  described  in  the  preceding  pages,  together 
with  the  fact  that  some  go  so  far  as  to  look  upon  pancreatic  diabetes 
as  really  an  adrenal  diabetes,  make  this  test  seem  not  irrational,  but 
it  certainly  does  not  yield  practical  results. 

The  interrelation  between  the  pancreas  and  spleen,  here  pub- 
lished for  the  first  time,  suggests  a  reason  for  Musser's  finding  of 
four  cases  of  acute  ansemia  among  eight  cases  of  acute  pancreatitis ;  39 
but  Musser's  findings  have  not  been  confirmed,  so  far  as  I  find,  perhaps 
because  his  findings  are  not  generally  known. 

The  second  group  of  tests,  those  showing  a  disturbance  of  the 
internal  secretion  which  controls  glucosuria,  seems  to  offer  the  greatest 
promise  of  practical  value,  judging  from  the  experiments  detailed 
under  the  discussion  of  the  factor  of  safety.  It  has  already  been 
pointed  out  that  glucosuria  alone  is  not  necessarily  indicative  of 
pancreatic  disease.  Three  factors  are  concerned  in  diabetes:  the 
pancreas,  the  liver,  and  the  muscles,  so  the  fault  need  not  necessarily 
lie  with  the  pancreas.  Glucosuria  with  acidosis — the  presence  of 
sugar  plus  acetone  and  /^-oxybutyria  acid  in  the  urine — is  thought  by 
some  to  represent  a  definite  indication  of  pancreatic  involvement,  but 
acidosis  is  a  late  symptom.  From  the  experiments  outlined  above  it 
would  seem  that  there  is  a  fairly  definite  relation  between  the  appear- 
ance of  glucose  in  the  urine  and  the  amount  of  pancreas  tissue  still 
functionating.  We  have  seen  that  there  is  no  disturbance  of  nitrogen 
intake,  neither  in  gross  amount  nor  in  the  rate  of  resorption.  There 
is  a  very  definite  and  sharp  line  marking  the  point  at  which  the  glu- 
cose^— either  the  glucose  fed  as  such  or  the  glucose  derived  from  the 
protein — ceases  to  be  completely  utilized  and  begins  to  appear  in  the 


48  INTERNATIONAL    CLINICS 

urine.  A  lowered  sugar  tolerance,  or,  better,  a  lowered  ability  to 
utilize  sugar,  seems,  therefore,  on  the  basis  of  our  experiments,  to  be 
the  most  hopeful  method  of  diagnosing  pancreatic  insufficiency. 

Where  the  Cammidge  test  belongs  in  the  above  classification  is 
doubtful,  or  even  if  it  is  a  test  relating  at  all  to  the  pancreas.  The 
physiological  chemists  have  never  taken  much  stock  in  it;  the  in- 
ternists find  it  positive  in  health  and  in  a  variety  of  diseases  in  which 
the  pancreas  is  normal,  and  negative  when  the  pancreas  is  extensively 
diseased.93  From  the  more  strictly  surgical  side,  the  reports  based 
on  the  extensive  material  of  the  Mayo  clinic  are  negative.96  The  test 
is  included  under  the  heading  of  the  internal  secretion,  since  Cam- 
midge very  recently  reports  97  that  the  substance  concerned  in  his  test 
is  dextrin. 

The  tests  designed  to  demonstrate  in  the  stomach  content,  the 
urine,  or  the  fseces  pancreatic  ferments  are  very  numerous.  Miiller 
and  Schlecht 98  introduced  the  serum-plate  method,  in  which  the 
presence  of  trypsin  in  the  fseces  is  revealed  by  the  digestion  of  the 
surface  of  a  serum-sugar  plate,  producing  a  pitting.  Gross  "  bases 
his  test  on  the  precipitation  of  casein  from  an  alkaline  solution  on 
acidifying  with  acetic  acid;  casein  digested  by  trypsin  does  not 
precipitate.  Pratt 93  records  his  own  experience  with  these  tests,  and 
then  adds :  "  That  an  absence  of  trypsin  in  the  fseces  always  indicates 
disease  of  the  pancreas  is  doubtful.  No  trypsin  could  be  demonstrated 
in  the  fseces  of  one  of  the  workers  in  our  laboratory.  He  presented  no 
symptoms  of  disease." 

Trypsin  has  been  sought  in  the  duodenal  contents  obtained  by 
causing  a  regurgitation  of  the  duodenal  content  into  the  stomach  by 
administering  large  amounts  of  oil.100  This  method,  introduced  by 
Volhard,101  will  doubtless  be  superseded  by  the  more  exact  procedure 
of  using  the  Einhorn  bucket102  or  the  Einhorn  tube.103  The  final 
test  of  these  methods  which  I  would  consider  definite,  to  find  in  a 
given  animal  if  the  trypsin  content  of  the  duodenum  after  a  given 
meal  and  a  given  time  were  constant,  then  to  remove  a  part  of  the 
pancreas  and  repeat  the  test,  seems  to  be  still  lacking. 

A  study  of  the  diastase  of  the  fseces  may  be  followed  by  the  method 
of  Wohlgemuth,104  with  numerous  modifications.  Reports  concern- 
ing the  value  of  this  test  are  inconclusive.  Recently  Y.  Noguchi 105 
and  Y.  JSToguchi  and  Wohlgemuth  106  report  the  finding  of  diastase 


SURGERY  OF  THE  PANCREAS  49 

in  the  blood  and  urine  of  dogs  with  experimental  pancreatic  injury, 
and  claim  that  the  amount  of  diastase  is  in  direct  relation  to  the 
extent  of  the  injury.     Clinical  confirmation  is  still  wanting. 

Opie's  one  case  107  of  the  finding  of  lipase  in  the  urine  in  acute 
pancreatitis  wanders  still  alone  and  unsupported  through  the  liter- 
ature, although  Hewlett108  showed  experimentally  that  lipase  can  be 
found  after  obstruction  of  the  pancreatic  duct  or  after  acute  pancre- 
atitis. The  demonstration  of  an  increase  in  the  ethereal  sulphates  of 
the  urine  is  supposed  to  depend  upon  a  lessened  growth  of  intestinal 
bacteria  when  the  pancreatic  juice  is  absent.109 

The  pioneer  of  the  tests  of  pancreatic  function  by  examining  the 
fasces  for  substances  which  are  supposed  to  be  digested  by  pancreatic 
juice  only  is  the  Schmidt's  nuclei  test.21 

It  was  pointed  out,  in  discussing  the  pancreatic  nuclease  under 
physiology,  that  the  stomach  can  digest  a  certain  amount  of  nucleins,22 
and  so  can  the  succus  entericus.23,  24  This  test  has  seen  various 
modifications,  which  may  generally  be  taken  to  mean  that  the  test  is 
not  entirely  satisfactory.  A  similar  test  is  that  of  Sahli,110  who  gave 
glutoid  capsules — gelatin  capsules  treated  with  formalin,  which  are 
not  supposed  to  be  digested  by  the  gastric  juice — filled  with  a  sub- 
stance, such  as  salol  or  iodoform,  which  can  readily  be  detected  in 
the  urine. 

These  tests  are  all  grossly  qualitative,  and  in  all  of  them  a  proper 
valuation  of  the  various  factors  concerned  is  difficult,  if  not  actually 
impossible.  It  is  interesting  to  note  the  conclusions  of  some  of  the 
writers  who  have  been  most  enthusiastic.  Thus  Pratt  concludes93: 
"  Pancreatic  insufficiency,  even  of  mild  degree,  can  be  recognized  by 
the  functional  methods  of  diagnosis  now  available.  At  the  present 
time  no  single  sign  or  symptom  can  be  accepted  as  pathognomonic  of 
pancreatic  disease,  but  by  the  use  of  a  number  of  different  tests  the 
diagnosis  can  be  made. 

"  The  functional  tests  have  already  thrown  much  light  on  the 
pathological  physiology  of  the  pancreas.  Observations  made  with 
these  tests  indicate  that  the  diminished  or  altered  secretion  of  the 
pancreas  may  occur  without  demonstrable  anatomical  change." 

Vautrain,89  apparently  disregarding  these  functional  tests,  writes : 
"  Les  symptomes  de  la  pancreatite  clironique,  aujourdhui  bien  encore 
mal  degages  et  insuffisamment  connus,  se  grouperont  bientot  pour  con- 
stituer  un  tableau  clinique  defini,  grace  auquel  le  diagnostic  sera  plus 


50  INTERNATIONAL    CLINICS 

facile.  On  decelera  alors  la  pancreatite  chronique  simple,  que  Von 
trouvera  frequemment  independente  de  toute  lithiase  biliaire,  et  car- 
acterisee  surtout  par  une  tumefaction  epigastrique,  un  peu  d'ictere,  des 
douleurs,  des  troubles  digestifs,  des  nausees  ou  des  vomissements, 
V amaigrissement  et  meme  la  cachexie." 

The  conservative  diagnosis  of  idiopathic  chronic  pancreatitis  will 
therefore  probably  not  often  be  made  until  some  real  functional  test 
of  the  pancreas  has  been  discovered.  Since  the  majority  of  cases  are 
secondary  to  infections  of  the  bile-tracts,  the  diagnosis  will,  by  the 
majority  of  surgeons,  be  ventured  only  in  those  cases  in  which  the 
symptoms  of  cholangitis  are  associated  with  a  palpable  mass  in  the 
region  of  the  head  of  the  pancreas,  or  even  to  those  cases  in  which, 
during  the  course  of  operation  upon  the  bile-passages,  the  head  of  the 
pancreas  is  found  to  have  a  consistence  differing  from  that  of  the  body 
of  the  gland.  The  more  enthusiastic  surgeon  will  be  inclined  to 
diagnose  the  condition  on  the  grounds  of  the  presence  of  a  mass  in  the 
pancreatic  region  plus  the  symptoms  of  serious  digestive  disturbance. 
And,  finally,  the  enthusiast  will  diagnose  the  disease  in  all  abdominal 
conditions  in  which  the  infection  of  the  lymph-channels  might  be 
reasonably  expected;  but,  while  we  shall  know  of  the  cases  he  finds 
positive,  we  will  never  learn  the  number  of  false  diagnoses  he  has 
made  in  the  course  of  his  series.  It  is  probably  particularly  true  of 
the  pancreas  that  our  knowledge  would  be  most  effectively  advanced 
if  all  the  failures  of  diagnosis  and  of  operative  treatment  were  frankly 
reported. 

The  matter  of  the  diagnosis  of  acute  pancreatitis  stands  on  an 
entirely  different  basis.  We  are  dealing  with  a  condition  in  which 
early  operation  offers  the  only  chance  for  the  patient,  and  in  which 
the  differential  diagnosis  concerns  only  conditions  which  can  like- 
wise be  treated  only  by  operative  measures.  While  the  differential 
diagnosis  between  acute  pancreatitis  and  ruptured  stomach  or  duo- 
denum or  gall-bladder  might  often  be  easily  made  on  the  basis  of  the 
case  history,  it  would  serve  no  purpose  to  delay  operation  in  order  to 
accomplish  it.  The  number  of  cases  which  have  been  opened  for 
high  obstruction  with  the  finding  of  acute  pancreatitis,  and  the  reverse, 
together  with  the  facts  brought  out  in  the  preceding  pages  which  tend 
to  prove  that  the  symptoms  of  high  obstruction  and  of  acute  pan- 
creatitis are  the  same,  because  they  are  due  to  the  same  toxic  agent, 
fully  demonstrates  the  impossibility  of  a  differential  diagnosis.     The 


SURGERY  OF  THE  PANCREAS  51 

only  hope  in  either  condition  is  immediate  operation.  So  soon  as  the 
belly  is  opened  the  diagnosis  may  sometimes  be  definitely  made  by  the 
discovery  of  fat  necrosis,  which  is  the  only  absolute  symptom  of  pan- 
creatic disease;  the  finding  of  a  peculiar,  dirty  fluid  is  suggestive; 
the  examination  of  the  pancreas  establishes  the  diagnosis. 

PANCREATOENTEROSTOMY 

In  1909,  Coffey  U1  published  the  result  of  experiments  designed 
to  provide  an  exit  into  the  intestine  for  the  pancreatic  juice  in  cases 
in  which,  for  one  reason  or  another,  such  as  malignant  disease  of  the 
head  of  the  pancreas,  or  of  the  common  duct,  etc.,  it  would  be  desir- 
able to  completely  remove  the  head  of  the  pancreas.  His  operation, 
which  he  named  pancreato-enterostomy,  consists  in  uniting  a  U-loop 
of  intestine  after  the  manner  of  a  Finney  pyloroplasty,  and  anas- 
tomosing the  pancreas  into  this  loop.  The  same  idea  was  worked  out 
in  this  laboratory,  but  with  a  much  more  simple  technic.  The  pro- 
cedure we  adopted  was  simply  to  sew  the  cut  end  of  the  pancreas  into 
a  longitudinal  slit  in  the  intestine.  As  shown  in  Fig.  15,  the 
pancreas  of  the  dog  is  an  extremely  elongated  organ,  admirably  suited 
to  such  an  operation.  The  end  of  the  uncinate  process  of  the  pancreas 
was  cut  off,  as  at  A,  Fig.  15;  the  end  of  the  pancreas  was  then 
attached  to  the  gut  by  a  row  of  fine  Lembert  sutures,  placed  at  a 
little  distance  from  the  cut  end  around  the  part  which  would  later  lie 
underneath  the  pancreas.  This  stitch  compares  to  the  first  row  of 
stitches  in  a  gastro-enterostomy.  A  longitudinal  slit  is  then  made 
through  the  wall  of  the  intestine,  the  end  of  the  pancreas  is  tucked 
into  the  slit,  and  the  Lembert  stitches  continued  around  the  pancreas 
to  the  point  of  beginning — comparable  to  the  fourth  row  of  a  gastro- 
enterostomy. The  operation  is  precisely  that  of  an  end-to-side  in- 
testinal anastomosis,  excepting  only  the  fact  that  the  end  of  the 
pancreas,  corresponding  to  the  end  of  gut  in  an  end-to-side  anastomo- 
sis, is  tucked  into  the  lumen  of  the  gut,  instead  of  being  simply 
approximated  to  the  wall.  The  results  of  these  experiments  were 
as  follows: 

In  a  series  of  three  dogs  the  uncinate  process  was  cut  off  at  A, 
Fig.  15,  and  the  duct  of  the  proximal  end  ligated.  The  cut  end  of 
the  distal  portion  of  the  pancreas  was  implanted  into  the  gut  by  the 
method  described.     All  three  showed  an  uneventful  and  perfect  clin- 


52 


INTERNATIONAL,    CLINICS 


ical  recovery;  autopsies  after  six,  five,  and  four  weeks,  respectively, 
showed  that  the  duct  was  patulous  in  all  three  dogs  and  of  normal 
size.  There  was  no  fat  necrosis,  no  evidence  of  leakage  or  suppura- 
tion, and  few  adhesions.     In  two  there  was  no  atrophy  of  pancreatic 


Fig.   17. 


Pancreato-enterostomy.     The  pancreas,  after  amputation  of  the  uncinate  process,  being  fastened 
to  the  wall  of  the  intestine  by  a  running  Lembert  suture. 


tissue ;  one  showed  a  shrinkage  to  one-third  of  the  original  size  of  the 
transplanted  piece. 

In  a  second  series  of  three  dogs  both  ducts  were  tied  with  double 
ligatures  and  cut  between  the  ligatures.  Instead  of  transplanting  the 
duct  of  the  uncinate  process,  the  uncinate  process  was  amputated  and 
the  proximal  end  of  the  pancreas  was  anastomosed  with  the  gut  in 
the  manner  described  above  (Figs.  17,  18,  and  19).  Two  of  these 
dogs  were  killed  and  autopsied  live  weeks  after  operation;   both 


SURGERY  OF  THE  PANCREAS 


53 


had  made  an  uneventful  recovery  and  had  shown  no  clinical  symp- 
toms; in  both  cases  a  new  duct  had  formed  about  the  double 
ligatures  of  the  main  pancreatic  duct,  and  the  implanted  duct  was 
not  patulous.  There  was  no  evidence  of  fat  necrosis,  leakage,  or  sup- 
puration, or  of  pancreatitis  or  atrophy.     The  third  dog  of  this  series 


Fig.  18. 


Pancreato-enterostomy.    The  first  row  of  Lembert  sutures  is  completed  and  the  gut  incised. 

died  a  week  after  operation  from  distemper  pneumonia.  The  autopsy 
showed  a  perfect  operative  result,  except  that  even  in  this  short  space 
of  time  a  new  duct  had  formed  about  the  ligatures. 

In  a  third  series  of  two  dogs  the  re-formation  of  the  ducts  was 
prevented  by  ligating  in  two  places,  cutting  between  the  ligatures, 
and  then  drawing  omentum  between  the  cut  ends  of  the  duct.     The 


54 


INTERNATIONAL    CLINICS 


proximal  end  of  the  pancreas  was  then  anastomosed  with  the  intestine 
as  in  series  2.  Four  weeks  after  the  operation,  which  was  followed 
by  uneventful  recovery,  the  autopsy  showed  that  the  implanted  duct 
was  patulous,  the  ligated  ducts  permanently  closed;  there  was  no 
atrophy  of  the  pancreas,  the  gland  showed  normal  consistence,  there 
were  no  evidences  of  fat  necrosis  or  leakage  or  suppuration,  and  few 
adhesions.     The  technic  in  the  third  dog  of  the  series  was  slightly 


Fig.  19. 


Pancreatoenterostomy.  The  ends  of  the  pancreas  have  been  tucked  into  the  slit  of  the  intes- 
tinal wall,  and  the  Lembert  suture  has  been  continued  to  the  point  of  beginning.  The  small  sketch 
shows  the  appearance  of  the  completed  operation  from  the  inside  of  the  intestine. 

varied ;  the  cut  end  of  the  pancreas  was  implanted  in  a  cut  of  the 
bowel  wall  which  extended  only  to  the  mucosa,  since  we  wished  to 
find  if  the  pancreas,  by  virtue  of  the  digestive  action  of  its  secretion, 
would  provide  an  escape  for  itself  through  the  mucosa.  The  animal 
died  at  the  end  of  a  week,  and  the  autopsy  showed  that  the  digestive 
action  of  the  secretion  was  indeed  present,  but  that  it  had  turned 
upon  the  pancreas  itself.  Sufficient  necrosis  or  autolysis  of  the  cells 
of  the  cut  end  of  the  pancreas  had  developed  to  activate  the  tryp- 


SURGERY  OF  THE  PANCREAS 


55 


sinogen — or  possibly  enterokinase  had  gained  entrance  from  the  cells 
of  the  mucosa — the  result  being  acute  pancreatitis  marked  by  fat 
necrosis,  and  death. 

This  same  operation  was  performed  on  another  animal  on  Decem- 
ber 13,  1913.     On  November  14,  1914,  the  animal,  which  was  in 


Fig.  20. 


The  result  of  the  operation  of  pancreatoenterostomy,  eleven  months  after  operation;  drawing 
of  Kaiserling  specimen,  a.  Probe  in  the  closed  papilla  of  the  main  duct.  6.  Double  loop  of  silk- 
worm-gut, passing  through  the  new  opening  of  the  duct  and  out  through  the  duct,  which  had  been 
slit  open  to  see  if  it  had  become  dilated. 

perfect  health,  was  autopsied  in  order  to  determine  the  result  of  the 
operation.     The  pancreas  was  entirely  normal,  the  original  duct  was 
closed,  and  the  new  duct  opening  of  ample  size  was  found  at  the  bot- 
tom of  a  little  dimple  of  the  intestinal  wall  (Fig.  20). 
The  results  of  these  experiments  show  that: 

1.  There  are  no  valves  in  the  pancreatic  ducts,  and  the  flow  can 
be  reversed. 

2.  Nature  is  surprisingly  insistent  that  the  normal  exit  be  pre- 


56  INTERNATIONAL    CLINICS 

served,  and  will  quickly  overcome  even  the  barrier  of  a  double  ligature 
and  excision  between  the  ligatures. 

3.  The  entire  pancreas,  or  a  portion  of  the  pancreas,  can  be 
joined  to  the  intestine  without  danger  of  pancreatitis,  either  chronic 
or  acute,  and  without  danger  of  sclerosis  for  so  long  as  eleven  months. 

4.  Ascending  infection  of  the  pancreas  is  certainly  not  prevented 
by  the  assumed  valve  action  of  the  sphincter  of  the  papilla,  or  the 
assumed  mechanical  valve  action  of  the  papilla  itself ;  nor  is  it  likely, 
in  view  of  these  experiments,  that  infection  ascends  up  the  lumen  of 
the  duct,  or  that  it  ascends  upwards  along  the  mucosa  of  the  duct. 

This  operation,  therefore,  taken  in  conjunction  with  the  facts 
presented  under  the  heading  of  the  factor  of  safety,  lead  to  the  con- 
clusion that  at  least  two-thirds  of  the  pancreas  could  be  safely  removed 
and  the  duct  of  the  remaining  portion  could  be  safely  and  simply 
anastomosed  to  the  intestine.  The  human  pancreas  is,  of  course, 
larger  in  proportion  to  the  human  intestine  than  is  the  pancreas  of 
the  dog  in  proportion  to  the  dog's  intestine ;  but  the  study  of  the  ex- 
periments described  above  leads  me  to  the  conclusion  that  the  pancreas 
could  be  safely  anastomosed  to  an  opening  of  the  intestine,  even 
though  the  end  of  the  pancreas  did  not  project  into  the  intestinal 
lumen  as  in  these  experiments. 

THE  SURGERY  OF  THE  PANCREAS 

If  the  method  of  reasoning  which  has  now  brought  us  to  the  ques- 
tion of  the  actual  surgical  procedure  is  logical  and  correct  in  its  basic 
ideas,  the  discussion  of  the  surgery  of  the  pancreas  can  be  reduced 
to  simple  terms.  If  we  agree  that  chronic  pancreatitis  is  a  lymph- 
angitis secondary  to  some  primary  focus  outside  the  pancreas,  then 
the  primary  focus  must  be  found  and  treated.  If  we  agree  that  the 
fatal  element  in  acute  pancreatitis  is  the  active  proteolytic  ferment  of 
the  pancreas,  which  ferment  is  made  active  by  the  addition  of  a 
product  which  develops  on  autolysis  of  the  gland  substance,  then  two 
things  must.be  always  borne  in  mind — prevention  of  the  autolysis  of 
the  pancreas  tissue  which  would  liberate  the  activating  factor,  and 
thorough  drainage  of  the  pancreatic  secretion  which  may  have  escaped 
into  the  surrounding  tissue ;  or,  in  simpler  terms,  removal  of  infection 
or  drainage,  and  prevention  of  the  escape  of  the  secretion  of  the  gland ; 
or,  if  it  has  already  escaped  from  its  normal  confines,  drainage. 
More  than  ordinary  care  must  be  used  to  prevent  tying  off  bits  of 


SURGERY  OF  THE  PANCREAS  57 

gland  tissue  with  ligatures.  Drainage  is  more  fundamental  with  the 
pancreas  than  with  any  other  organ ;  not  only  an  infection  must  be 
drained,  but  also  the  normal  product  of  the  organ.  A  study  of  the 
reports  of  the  operative  procedures  on  the  pancreas  will  establish  the 
truth  of  this  reasoning,  even  though  these  procedures  have  not  always 
been  based  on  a  clear  concept  of  the  principles  involved. 

Let  us  begin  with  the  more  simple  surgical  operations,  rather  than 
follow  the  usual  method  of  beginning  with  the  more  simple  patho- 
logical conditions. 

We  find  all  surgeons  agreed  that  a  drainage  of  the  biliary  system 
represents  the  curative  procedure  in  chronic  pancreatitis.  We  have 
seen  that  a  simple  drainage  of  the  gall-bladder  cannot  necessarily 
drain  the  pancreatic  ducts,  even  if  the  infection  had  ascended  the 
lumen  of  the  ducts,  since  the  mode  of  development  of  the  ducts  and 
their  diverse  manner  of  entering  the  duodenum  may  make  it  a 
physical  impossibility  to  drain  the  pancreas  in  this  manner  (Fig.  7). 
But,  furthermore,  agreeing  that  chronic  pancreatitis  is  a  lymph- 
angitis, we  must  agree  that  the  infection  is  a  deeper  lying  one 
than  the  mucosa  of  the  gall-bladder  or  the  mucosa  of  the  ducts;  it 
must  be  in  the  wall  of  the  bile-passages.  Therefore  we  may  disregard 
the  various  propositions  which  have  been  made,  exploratory  laparot- 
omy alone,  or  drainage  of  the  gall-bladder,  or  cholecystenterostomy, 
or  cholecystogastrostomy  (Jaboulay  112),  the  reason  being  perfectly 
clear  why  Mayo  reports: 113 

"  In  at  least  one-half  of  the  cases  operated  on  in  our  clinic  the 
following  sequence  has  occurred :  cholecystostomy  had  been  done  for 
chronic  cholecystitis  without  stones,  and  with  a  complicating  chronic 
pancreatitis.  The  patient  was  relieved  for  some  weeks  or  months  and 
then  the  symptoms  returned.  Recognizing  the  need  of  more  pro- 
longed drainage,  the  gall-bladder  was  reopened  and  drained  for  a 
considerable  period.  There  was  complete  relief  so  long  as  drainage 
of  the  gall-bladder  continued,  but  sooner  or  later,  after  the  fistula  in 
the  gall-bladder  healed,  the  symptoms  returned. 

"  These  cases  are  characteristic,  and  I  have  no  doubt  have  been 
observed  by  many  surgeons  who  have  been  puzzled  to  know  just  what 
course  to  pursue.  It  has  been  our  experience  that  removal  of  the 
gall-bladder  primarily  relieves  the  symptoms  and  permanently  cures 
the  patient.  Just  what  the  future  condition  of  the  pancreas  may  be 
one  has  no  means  of  knowing,  but  I  have  found  that  chronic  pancre- 


58  INTERNATIONAL    CLINICS 

atitis,  the  result  of  gall-stone  disease,  is  usually  cured  by  the  removal 
of  the  stones  and  drainage  of  the  biliary  tract,  and  that  in  the  chronic 
infection  of  the  gall-bladder  with  secondary  involvement  of  the 
pancreas,  in  the  absence  of  infections  with  biliary  drainage,  chole- 
cystotomy  furnishes  a  satisfactory  symptomatic  cure." 

The  proper  procedure  in  so-called  idiopathic  chronic  pancreatitis 
is  not  clear,  nor  will  it  be  clear  until  we  are  agreed  whether  such  a 
condition  really  exists.  I  personally  suspect  that  all  cases  of  chronic 
pancreatitis  represent  a  chronic  lymphangitis  secondary  to  some  other 
focus  of  infection;  primary  infection  of  the  glandular  tissue  of  the 
pancreas  would  lead  to  suppuration  with  certain  microorganisms, 
while  with  others  it  would  lead  to  necrosis,  autolysis,  activation  of 
trypsinogen,  and  acute  pancreatitis.  There  is  certainly  no  reason 
why  the  numerous  lymph-channels,  anastomosing  with  surrounding 
structures,  should  not  carry  infection  toward  the  pancreas  as  well  as 
do  the  lymphatics  of  the  bile-tracts.  The  role  played  by  a  small  stone 
lodged  in  the  ampulla  of  Vater  in  the  production  of  both  chronic  and 
acute  pancreatitis  justifies  the  routine  careful  examination  of  the 
ampulla,  even  to  the  extent  of  direct  examination  through  an  incision 
of  the  duodenum. 

We  have  seen  that  acute  pancreatitis  can  only  be  explained  by 
the  facts  of  the  activation  of  the  proteolytic  proferment.  We  have 
seen  that  this  activation  can  be  brought  about  by  the  enterokinase 
of  the  intestine  or  by  a  product  formed  on  the  autolysis  of  the  gland 
itself,  and  that  the  inactive  juice  is  not  toxic.  A  consideration  of 
these  facts  makes  clear  the  surgical  procedures  indicated  when 
handling  the  pancreas — to  avoid  trauma  which  might  result  in 
autolysis,  to  prevent  the  escape  of  pancreatic  secretion,  which,  while 
itself  harmless,  might  become  activated,  and,  in  the  presence  of 
activated  secretion,  acute  pancreatitis,  to  provide  ample  opportunity 
for  its  escape — thorough  drainage. 

We  find  in  the  report  of  von  Mikulicz  114  the  records  of  75  cases 
of  operation  for  acute  pancreatitis,  in  36  of  which  the  pancreas  was 
directly  attacked,  with  25  recoveries,  while  in  41  where  the  pancreas 
was  not  attacked  only  4  recovered,  and  in  these  free  drainage  was 
provided.  In  other  words,  the  toxic  product  is  not  in  the  peritoneal 
cavity,  but  in  the  gland,  and  a  means  of  escape  for  it  must  be  provided. 

If  we  feel  that  such  statistical  records  are  of  doubtful  value,  since 
it  is  impossible  to  compare  the  work  of  different  surgeons,  even  in  the 


SURGERY  OF  THE  PANCREAS  59 

same  field,  let  us  turn  to  Korte,40  who  has  had  the  largest  experience 
in  acute  pancreatitis  of  any  single  surgeon.  His  opinion,  based  on 
the  study  of  44  cases,  is  expressed  as  follows : 

"  So  empfehlen  jetzt  die  meisten  Chirurgen,  das  entzundete 
Pankreas  freizulegen.  Wahrend  nun  Einige  sich  damit  begnugen 
wollen,  nur  die  Oberflache  desselben  durch  Gaze  und  Rohr  zu 
drainiren,  rathen  Andere,  in  das  erkrankte  Organ  einzudringen.  Wie 
ich  oben  auseinandergesetzt  habe,  schliesse  ich  mich  den  Letzteren  an 
und  glaube,  dass  man  dadurch  die  Entzundung  mildern  und  ausge- 
dehnterem  Absterben  vorbeugen  kann." 

As  to  the  time  of  operation,  there  can  be  no  doubt,  on  the  basis  of 
the  reasoning  thus  far  followed,  that  the  earlier  the  operative  inter- 
ference, the  better.  The  destructive  process  once  started  may  un- 
doubtedly be  limited  and  walled  off  by  nature,  though  it  may  just  as 
well  involve  the  whole  gland,  and  there  can  certainly  be  no  way  of 
determining  the  extent,  or  of  limiting  the  extent,  except  by  operation. 
Definite  information  on  this  point  is  given  by  Korte  40 ;  of  sixteen 
cases  operated  within  the  first  two  weeks  after  the  beginning  of  the 
disease,  eleven  recovered  and  five  died.  Of  the  fourteen  operated 
within  the  third  and  fourth  weeks,  seven  recovered  and  seven  died. 
The  four  operated  in  the  fifth  to  the  sixth  week  all  died.  Deaver 1 15 
would  not  undertake  operation  in  the  state  of  primary  shock.  Because 
of  the  experimental  results  in  high  obstruction  which  have  been 
described  in  the  preceding  pages,  and  because  of  the  relation  between 
the  pancreas  and  the  suprarenals,  and  the  role  of  the  suprarenals  in 
shock,  I  would  suggest  the  use  of  intravenous  saline  infusion  with 
adrenalin  in  dilution  in  the  saline  to  combat  this  shock  and  make 
operation  possible,  beginning  the  infusion  before  the  operation,  con- 
tinuing it  during  the  operation,  and  after  if  necessary. 

The  recognition  of  the  toxic  factor  in  the  pancreas  leads  to  the 
question  of  the  manner  of  treatment  of  pancreatic  cysts  and  of  wounds 
of  the  pancreas.  The  pseudocysts  of  the  pancreas  cannot  be  extirpated, 
since  their  walls  are  formed  from  the  tissues  of  the  parts  adjacent  to 
the  pancreas;  they  can  be  attached  to  the  parietes  and  drained — 
"  marsupialized."  True  cysts — cysts  in  connection  with  the  ducts 
of  the  pancreas — must  be  extirpated,  since  if  drained  they  leave  fistulse 
which  will  not  close  (Korte116). 

The  treatment  of  wounds  of  the  pancreas  must  be  conducted  on 


60  INTERNATIONAL    CLINICS 

the  same  lines.  Given  a  case  of  complete  transverse  rupture,  which 
cases  are  fairly  numerous  in  the  literature,12,  13, 14  the  only  rational 
treatment  would  consist  in  either  complete  removal  of  the  distal 
portion  of  the  gland,  which,  as  we  have  seen  in  the  discussion  of  the 
factor  of  safety,  is  a  perfectly  rational  surgical  suggestion ;  or  else, 
since  technically  this  is  no  easy  suggestion,  I  would  propose  the  liga- 
tion of  both  ends  of  the  torn  duct.  The  distal  portion  of  the  gland 
itself,  having  been  ligated,  would  suffer  sclerosis  of  the  excreting 
cells,  while  enough  of  the  elements  of  the  pancreas  would  persist  to 
aid  in  the  preservation  of  the  internal  functions  of  the  pancreas,  as 
we  have  seen  in  the  preceding  discussion  of  the  experiments  in  which 
the  external  function  of  the  pancreas  was  completely  removed.  The 
traumatized  portions  of  the  gland  should  be  carefully  removed  and 
drainage  should  be  carried  to  the  pancreatic  stumps,  either  through 
an  anterior  excision,  or,  perhaps,  even  better,  drainage  would  be  more 
thorough  by  draining  through  a  stab  wound  through  the  back. 

The  importance  of  removing  traumatized  tissue  has  several  times 
been  made  evident  in  our  experiments  upon  the  complete  removal 
of  the  external  function  of  the  pancreas.  I  have  seen  a  fatal  pancre- 
atitis which  evidently  started  in  the  portion  of  the  gland  which  had 
been  exposed  to  autolysis  by  the  ligature  which  tied  the  duct. 

The  procedure  to  be  followed  in  dealing  with  tumors  of  the 
pancreas  is  undoubtedly,  as  elsewhere  stated,  complete  extirpation. 
The  location  of  the  pancreas  itself  and  the  involved  anatomical  rela- 
tions; the  free  anastomoses  of  its  lymphatics  with  so  many  regional 
lymph-nodes,  together  with  the  late  time  of  diagnosis,  make  the  hope 
of  early  radical  removal  of  carcinoma  seem  very  remote.  The  opera- 
tion of  pancreatoenterostomy  described  above  offers  a  solution  for 
the  treatment  of  non-malignant  tumors  of  the  head  of  the  pancreas,  as 
well  as  the  suggestion  for  the  symptomatic  treatment  of  malignant 
tumors  in  which  secondary  symptoms  of  pressure  might  justify  a 
palliative  procedure. 

CONCLUSIONS 

Our  inventory  is  complete.  On  assembling  our  notes  of  stock  on 
hand,  we  find  that  the  pancreas  is  an  admirably  protected  and  there- 
fore surgically  difficult  organ. 

The  factor  of  safety  is  high,  so  that  removal  of  two-thirds  of  the 
pancreas,  at  least,  and  probably  more,  is  perfectly  possible,  the  only 
difficulty  being  one  of  technic. 


SURGERY  OF  THE  PANCREAS  61 

This  very  factor  of  safety  makes  it  clear  that  the  tests  of  the  func- 
tional activity  of  the  pancreas  can  hardly  be  expected  to  be  of  much 
value  in  the  diagnosis  of  early  pancreatic  involvement. 

The  duct  of  the  pancreas  can  be  transplanted  without  danger  of 
an  ascending  infection. 

Chronic  pancreatitis  is  a  lymphangitis,  probably  always  secondary 
to  a  focus  of  infection  in  some  neighboring  organ,  the  lymph-vessels 
of  which  anastomose  with  the  lymph-vessels  of  the  pancreas.  The 
treatment  of  chronic  pancreatitis  is  therefore  the  surgical  removal 
of  the  primary  focus  of  infection. 

Acute  pancreatitis  is  a  disease  process  determined  by  the  terrible 
digestive  power  upon  the  tissues  of  the  living  body  of  the  proteolytic 
ferment  of  the  pancreas,  which  ferment  may  be  set  free  and  trans- 
formed from  the  harmless  zymogen  stage  in  which  the  ferment  is 
normally  found  in  the  cells  and  ducts  of  the  pancreas  by  infection  or 
by  sterile  autolysis.  Infection  does  not  necessarily  produce  an  acute 
pancreatitis;  an  infection  which  caused  the  toxic  death  of  the  cells 
of  the  pancreas  would  compare  with  autolysis,  whereas  an  infection 
which  determined  the  complete  dissolution  of  the  cells  might  destroy 
the  zymogen  also,  and  result  in  suppuration  and  localized  abscess 
formation. 

We  find  in  this  consideration  of  the  pancreas  the  importance  to 
surgery  of  what  we  may  call  a  new  principle — the  avoidance  not  only 
of  the  septic  digestion  of  tissue,  but  also  the  avoidance  of  sterile  self- 
digestion,  or  autolysis.  Not  only  in  the  pancreas  but  in  the  brain  can 
a  fatal  process  be  loosed  by  autolysis :  in  the  pancreas,  acute  pancre- 
atitis; in  the  brain,  cerebral  softening,  as  after  cerebral  hemorrhage. 

The  prevention  of  autolysis  can  be  accomplished  by  avoiding 
trauma — the  direct  trauma  of  rough  handling  or  the  trauma  of  ligat- 
ing  a  mass  of  tissue  instead  of  the  actual  bleeding  vessel — and  by  the 
careful  removal  of  all  pancreatic  tissue  which  has  been  crushed  or  cut 
off  from  its  blood  supply. 

Once  started,  this  autolytic  process  and  its  consequent  setting  free 
of  the  protein-digesting  ferment  of  the  pancreas  can  be  treated  only 
by  drainage,  drainage  not  only  of  the  infection  which  may  have  been 
the  causative  factor,  but  drainage  of  this  digesting  fluid,  drainage  of 
the  gland  itself  and  of  the  tissues  into  which  the  secretion  of  the  gland 
has  penetrated. 


62  INTERNATIONAL    CLINICS 

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SURGERY  OF  THE  PANCREAS  63 

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Kircheim:  Arch.  f.  Exp.  Path.  u.  Pharm.,  1911,  66,  352. 

Kirste:  Nihrnberger  med.  Ges.,  December,  1902. 

Lattes:  Arch,  di  farmacol.  speriment.  e  sc.  aff.,  1912,  13. 

Lattes:  Pathologica,  1912. 

Lewit:  I.  Diss.  Konigsberg,  1906. 

Maragliano:   Policlinico  sez.  Chir.,  1912,  19,  49. 

v.  Mikulicz:   Grenzgeb.  d.  Med.  u.  Chir.,  1913,  26,  1. 

Polya:   B.  K.  W.,  1906,  49.     Pfluger's  Arch.,  1908,   121,  483.     Grenzgeb.  d. 
Med.  u.  Chir.,  1911,  24,  1. 

Roosen-Runge:  Zeitschr.  f.  klin.  Chir.,  1901,  45,  56. 

Rosenbach:  Arch.  f.  klin.  Chir.,  1911,  94,  2. 

Seidel:  38  Vers.  d.  d.  Ges.  f.  Chir.,  Berlin,  1909.    Zentralbl.  f.  Chir.,  1910,  51. 

Simmonds:  Munch.  Med.  Wochen.,  1898,  6. 
"Balser:  Virchow's  Archiv,  1882,  90,  520. 
45Erdmann:  Annals  of  Surgery,  58,  ii,  688. 
48  Kirste  :  Nurnberger  med.  Gesell.,  December,  1902. 
"Heinecke:  Arch.  f.  klin.  Chir.,  1907,  84,  4. 

^Erdmann:  Trans.  N.  Y.  Surg.  Soc,  May  14,  1913;  Ann.  of  Surg.,  58,  ii,  688. 
^Lattes:  Virchow's  Archiv,  1913,  211,  1. 

60Blume:  Festschrift  zur  Naturforcherversammlung,  Braunschweig,  1897. 
"Oser:  "Nothnagel's  Handbuch,"  etc.,  1898,  18. 
B2Milisch:  I.  Diss.  Berlin,  1897. 
53  Lewit:  /.  Diss.  Konigsberg,  1906. 
"Wolff:    Verhandl.  d.  Ges.  deutsch.  Naturforsch.  u.  Arzte,  71  vers.,  Miinchen, 

1899,  ii,  2,  550. 
65  Hess  :  Munch,  med.  Wochen.,  1903,  1905. 
bbGtjleke:  Arch.  f.  klin.  Chir.,  1906,  78,  44;  1908,  85,  43. 
"Eppinger:  Ztschr.  f.  exp.  Path.  u.  Ther.,  1905,  2,  216. 
08  Flexner:  Journ.  of  Exp.  Med.,  1897,  ii. 

59  Opie  :   "  Diseases  of  the  Pancreas." 

60  Polya:  B.  k.  W.,  1906,  49. 

61  Hlava  :  C.  R.  du  XII  Congres  Inter,  de  Med.,  Moscow,  1897. 

62  Flexner  and  Pearce:  V.  of  Penna.  Med.  Bull.,  1901,  94. 
83  Hildebrand  :  Arch.  f.  klin.  Chir.,  1898,  57. 
"Rosenbach:  Arch.  f.  klin.  Chir.,  1909,  89,  2. 

65  Carnot:  These  de  Paris,  1898. 

mThiroloix:  Bull,  de  Soc.  anat.  de  Paris,  1891,  573. 
"Panum:  Virchow's  Archiv,  1862,  25,  308. 
68Lepine:  Lyon  med.,  1892,  302. 


64  INTERNATIONAL    CLINICS 

69Bunge:  Arch.  f.  Mm.  Chir.,  1903,  71,  726. 

70  Katz  und  Winkler:  Arch.  f.  Verdangskrank.,  1898,  4. 

"Pawlow:  "The  Work  of  the  Digestive  Glands,"  London,  1902. 

72Lombkoso:  Giornale  del  ace.  di  med.  di  Torino,  1903,  66,  225. 

73  Roger  et  Garnier:  C.  R.  Soc.  Biol,  1905,  ii,  388,  674,  677. 

74Falloise:  Arch,  intern,  de  Phys.,  1905,  ii,  299. 

70  Cybulsky  et  Taschanoff:  Arch.  int.  de  Phys.,  1907,  5,  257. 

"Roger  et  Garnier :  C.  R.  Soc.  Biol.,  1908,  ii,  1910. 

"Fleig:  C.  R.  Soc.  Biol.,  1908,  ii,  718. 

78Seidel:  38  Vers.  d.  d.  Ges.  f.  Chir.,  Berlin,  1909. 

79  Kirschheim  :  Arch.  f.  exp.  Path.  u.  Pharm.,  1911,  66,  352. 

80  Schittenhelm  und  Weichardt  :   Miinch.  med.  Wochen.,  1911,  843. 

81  Fragoin  e  Stradiotti:  Arch,  per  le  Sc.  med.,  1910,  34,  38. 

82  Maragliano  :  Policlinico  sez.  chir.,  1912,  19,  49. 

83  Sweet:  Penna.  Medical  Journal,  April,  1913. 
84Halsted:  Am.  Journ.  Med.  Sci.,  1887,  94,  436. 

86  H'artwell  and  Hoguet:   Am.  Journ.  Med.  Sci.,  1912,  143,  357.     J.  A.  M.  A., 

1912,  59,  82. 
86Deaver  and  Pfeiffer:  Annals  of  Surgery,  1913,  58,  ii,  151. 

87  Coffey:  Annals  of  Surgery,  1909,  50,  1238. 

88  Sweet  and  Stewart:  Surg.,  Gyn.  and  Obst.,  April,  1914. 

89  Walther-Sallis  :  Rev.  di  Chir.,  1913,  48,  2,  907;  1914,  49,  1,  446. 
00  Nordmann  :  Arch.  f.  Min.  Chir.,  1913,  102,  66. 

91  Arnsperger:  Deutsch.  Ges.  f.  Chir.,  1913. 

82  Archibald  and  Mullally:  Canadian  Med.  Journ.,  February,  1913. 

98 Pratt:  Am.  Journ.  Med.  Sci.,  March,  1912. 

94  Pearce  :  Personal  communication. 

96  Sailer:  Am.  Journ.  Med.  Sci.,  1910,  140,  330. 
96Pilcher:  Annals  of  Surgery,  1910,  51,  89. 

Wilson:  Surg.  Gyn.  and  Obst.,  1910,  11,  156. 

97  Cammidge:  J.  A.  M.  A.,  1914,  63,  2063. 

98MtJLLER  und  Schlecht:  Munch,  med.  Wochen.,  1908,  55,  225. 

99  Gross  :  Arch.  f.  exp.  Path.  u.  Pharm.,  1907,  58,  157. 

100  Bold yreff  :  Centralbl.  f.  Phys.,  1904,  18,  457. 
101Volhard:  Miinch.  med.  Wochen.,  1907,  54,  403. 
102Einhorn:  N.  Y.  Med.  Journ.,  1908,  87,  1179. 
103Einhorn:   Med.  Rec,  1910  77,  98. 

104  Wohlgemuth  :  Biochem.  Zeitschr.,  1909,  30,  432. 
105Noguchi,  Y.:  Langenbeck's  Archiv,  xcviii,  Heft  2. 
106Noguchi,  Y.,  und  Wohlgemuth:  B.  'k.  W.,  1912,  No.  23. 
10TOpie:  Johns  Hopkins  Hosp.  Bull.,  1902,  18,  117. 
108  Hewlett:  Journ.  Med.  Res.,  1904,  6,  377. 
109Tileston:  Trans.  Ass.  Am.  Phys.,  1911,  26,  522. 
U0Sahli:  Deutsch.  med.  Wochen.,  1897,  23,  6. 
111  Coffey  :  Annals  of  Surgery,  1909,  50,  1238. 
U2Jaboulay:  Lyon  Med.,  1898. 

113 Mayo,  W.  J.:  Am.  Journ.  Med.  Sci.,  1914,  147,  469. 
114  Von  Mikulicz:  Annals  of  Surgery,  1903,  38,  1. 
1X5Deaver:  Am.  Journ.  Med.  Sci.,  1909,  138,  829. 
11gKorte:  Deutsch.  med.  Wochen.,  1914,  40,  424. 
U7Loewi:  Arch.  f.  exp.  Path.  u.  Pharm.,  1909,  59,  83. 


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